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Wang X, Song SM, Lu WQ, Zhao Y, Lv RJ, He Y, Dong N, Yu Q, Yue HM. Alpha-lipoic acid alleviated intermittent hypoxia-induced myocardial injury in mice by promoting autophagy through Nrf2 signaling pathway. Eur J Pharmacol 2025; 994:177380. [PMID: 39954840 DOI: 10.1016/j.ejphar.2025.177380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 02/06/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
Obstructive sleep apnea syndrome (OSAS) is a prevalent sleep-related breathing disorder characterized by intermittent hypoxia (IH). Myocardial injury is a common complication associated with OSAS. Alpha-lipoic acid (LA), a potent antioxidant, has been utilized in various disease contexts and has demonstrated significant protective effects in myocardial infarction models. Given the limited treatment options available for OSAS-related myocardial injury, this study aimed to demonstrate the potential therapeutic effects of LA and to investigate the underlying mechanisms. IH is a widely employed method to simulate the pathophysiological conditions associated with OSAS. In vivo experiments were conducted using mice placed in a specialized hypoxic chamber to replicate IH conditions. Echocardiography indicated that exposure to IH severely impaired cardiac function. Treatment with LA activated the Nrf2 pathway and autophagy, which contributed to the improvement of cardiac function in mice with OSAS. Additionally, in vitro studies demonstrated that IH induced apoptosis and decreased cell viability in H9C2 cardiomyocytes. LA enhanced Nrf2 nuclear translocation and its downstream signaling pathways, thereby promoting autophagy, inhibiting apoptosis, and alleviating injury in H9C2 cardiomyocytes. Furthermore, in vitro inhibition of Nrf2 using ML385 reduced autophagy levels and attenuated the protective effects of LA against apoptosis in H9C2 cardiomyocytes. These findings suggest that LA may provide a promising therapeutic strategy for myocardial injury associated with OSAS. By elucidating these findings, new insights into the protective mechanisms of LA against IH-induced myocardial injury are provided, highlighting its potential as a therapeutic agent for diseases associated with OSAS.
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Affiliation(s)
- Xiao Wang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Shao-Ming Song
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Wen-Qiang Lu
- Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Yan Zhao
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Ren-Jun Lv
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Yao He
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Na Dong
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China; Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Qin Yu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China; Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
| | - Hong-Mei Yue
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China; Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
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Vafaee F, Derakhshani M, Ghasemzadeh Rahbardar M, Hosseinzadeh H. Alpha-lipoic acid, as an effective agent against toxic elements: a review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3345-3372. [PMID: 39556148 DOI: 10.1007/s00210-024-03576-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 10/27/2024] [Indexed: 11/19/2024]
Abstract
This review aims to evaluate the efficacy of alpha-lipoic acid (ALA) in combating toxic elements, such as aluminum, arsenic, lead, mercury, and cadmium. The primary research question addressed is whether ALA can effectively mitigate the toxic effects of these metals through its antioxidant and chelating properties. Articles published between 1995 and 2024 were collected from Scopus, PubMed, Google Scholar, and Web of Science. Using Boolean (AND and OR), English-language publications were selected based on medical subject headings, titles, or abstracts that contained keywords related to ALA, metals, toxicity, antioxidants, and chelation. ALA supplementation significantly enhances cellular defense mechanisms and antioxidant enzyme activity. It effectively mitigates the adverse effects of aluminum exposure, counters arsenic toxicity in various cells and organs, and reduces cadmium toxicity, resulting in lower mortality rates among treated groups. Although ALA acts as a lead chelator, its efficacy is less than standard chelators. In the case of mercury, ALA shows beneficial effects in long-term therapy, although its capacity to reduce mercury concentration is limited. Overall, ALA emerges as a promising alternative for alleviating metal toxicity by enhancing antioxidant defenses, chelating toxic metals, and reversing their harmful effects. Further research in this area is encouraged to explore the full potential of ALA in mitigating the toxic effects of metals on biological systems.
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Affiliation(s)
- Farzad Vafaee
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Derakhshani
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Hossein Hosseinzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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Lyu F, Hakariya H, Hiraoka H, Li Z, Matsubara N, Soo Y, Hashiya F, Abe N, Shu Z, Nakamoto K, Kimura Y, Abe H. Intracellular Delivery of Antisense Oligonucleotides by Tri-Branched Cyclic Disulfide Units. ChemMedChem 2024; 19:e202400472. [PMID: 38957922 DOI: 10.1002/cmdc.202400472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 06/26/2024] [Indexed: 07/04/2024]
Abstract
Therapeutic oligonucleotides, such as antisense DNA, show promise in treating previously untreatable diseases. However, their applications are still hindered by the poor membrane permeability of naked oligonucleotides. Therefore, it is necessary to develop efficient methods for intracellular oligonucleotide delivery. Previously, our group successfully developed disulfide-based Membrane Permeable Oligonucleotides (MPON), which achieved enhanced cellular uptake and gene silencing effects through an endocytosis-free uptake mechanism. Herein, we report a new molecular design for the next generation of MPON, called trimer MPON. The trimer MPON consists of a tri-branched backbone, three α-lipoic acid units, and a spacer linker between the oligonucleotides and tri-branched cyclic disulfide unit. We describe the design, synthesis, and functional evaluation of the trimer MPON, offering new insights into the molecular design for efficient oligonucleotide delivery.
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Affiliation(s)
- Fangjie Lyu
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Hayase Hakariya
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Haruka Hiraoka
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Zhenmin Li
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Noriaki Matsubara
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Yonghao Soo
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Fumitaka Hashiya
- Research Center for Materials Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Naoko Abe
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Zhaoma Shu
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Kosuke Nakamoto
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Yasuaki Kimura
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
| | - Hiroshi Abe
- Department of Chemistry, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
- Research Center for Materials Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan
- Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Aichi, 464-8601, Japan
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Superti F, Russo R. Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits. Antioxidants (Basel) 2024; 13:1228. [PMID: 39456481 PMCID: PMC11505271 DOI: 10.3390/antiox13101228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/26/2024] [Accepted: 10/09/2024] [Indexed: 10/28/2024] Open
Abstract
Alpha-lipoic acid (ALA) is a bioactive molecule with significant health effects. The biological action of ALA has been ascribed to the characteristic antioxidant properties of the oxidized form (ALA) and its reduced counterpart the dihydrolipoic acid (DHLA) system. The ALA/DHLA combination represents an ideal antioxidant since it can quench radicals, is able to chelate metals, is amphiphilic, and has no major adverse effects. This unique system is able to scavenge reactive oxygen species, exerting a major effect on tissue levels of reduced forms of other antioxidants, including glutathione. For this reason, ALA is also known as the "antioxidant of antioxidants". This review analyzes the antioxidant, anti-inflammatory, and neuroprotective effects of ALA and discusses its applications as an ameliorative tool for chronic diseases and those associated with oxidative stress. Results from in vitro and in vivo studies demonstrated that ALA modulates various oxidative stress pathways suggesting its application, alone or in combination with other functional substances, as a useful support in numerous conditions, in which the balance oxidant-antioxidant is disrupted, such as neurodegenerative disorders. Based on several successful clinical studies, it has been also established that oral ALA supplements are clinically useful in relieving the complications of diabetes and other disorders including cardiovascular diseases and nerve discomforts suggesting that ALA can be considered a useful approach to improving our health.
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Affiliation(s)
- Fabiana Superti
- Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, RM, Italy;
- Association for Research on Integrative Oncology Therapies, (ARTOI) Foundation, Via Ludovico Micara, 73, 00165 Rome, RM, Italy
| | - Rosario Russo
- Giellepi S.p.A., Via G. Verdi, 41/Q, 20831 Seregno, MB, Italy
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Dugbartey GJ, Atule S, Alornyo KK, Adams I. Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats. Biochem Pharmacol 2024; 227:116447. [PMID: 39038553 DOI: 10.1016/j.bcp.2024.116447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 06/26/2024] [Accepted: 07/18/2024] [Indexed: 07/24/2024]
Abstract
Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fasting blood glucose was measured. The rats were randomized into four groups: HC (healthy control; n = 7), T2DM (diabetic rats without treatment; n = 9), GLC (diabetic rats with 15 mg/kg gliclazide treatment; n = 7) and GLC+ALA (diabetic rats with gliclazide and 60 mg/kg ALA treatment; n = 7). T2DM was induced by a bolus administration of 110 mg/kg nicotinamide and 55 mg/kg streptozotocin intraperitoneally. The experimental protocol lasted for 6 weeks after which the animals were sacrificed and pancreas, liver and blood samples were collected for biochemical, histological and molecular analyses. Compared to healthy control (HC) group, exposure of HL-7702 cells to high glucose induced significant cell death by 19 % (p < 0.001), which was exacerbated with gliclazide treatment by 29 % (p < 0.0001) but markedly reduced by 6 % to near HC value following ALA treatment. In vivo, GLC-treated rats had severe liver damage characterized by increased hepatocellular vacuolation, and significant expression of ED-1, iNOS and caspase-3 as well as markedly high levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase compared to T2DM rats. Interestingly, ALA administration prevented these pathological changes and protected the diabetic liver to levels comparable to HC rats. ALA showed hepatoprotective effect against gliclazide-induced hepatotoxicity by suppressing inflammation and apoptosis while activating antioxidant pathway in the diabetic liver. Abbreviations: ALA, Alpha-lipoic acid; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; AMPK, Adenosine monophosphate-activated protein kinase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; DMEM, Dulbecco's Modified Eagle Medium; EDTA, ethylenediaminetetraacetic acid; FBG, Fasting blood glucose; FBS, Fetal bovine serum; GLC, Gliclazide; GLUT4, Glucose transporter type 4; GSH, Glutathione; H&E, Hematoxylin/Eosin; HbA1c, Glycosylated haemoglobin A1c; HC, Healthy control; HG, Hyperglycemic group; HOMA-β, Homeostasis model assessment of β-cell function; IL-1β, Interleukin-1β; IL-6, Interleukin-6; iNOS, Inducible nitric oxide synthase; KATP, ATP-dependent potassium channels; MDA, Malondialdehyde; MPTP, Mitochondrial permeability transition pore; NO, Nitric oxide; P/S, Penicillin/streptomycin; PAS, Periodic acid-Schiff; RIA, Radioimmunoassay; ROS, Reactive oxygen species; SOD, Superoxide dismutase; T2DM, Type 2 diabetes mellitus; TBARS, Thiobarbituric acid reactive substances; TNF-α, Tumor necrosis factor-alpha.
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Affiliation(s)
- George J Dugbartey
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana; Department of Physiology & Pharmacology, Accra College of Medicine, East Legon, Accra, Ghana.
| | - Stephen Atule
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Karl K Alornyo
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Ismaila Adams
- Department of Medical Pharmacology, University of Ghana Medical School, Korle-Bu, Accra, Ghana
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Jovičić-Bata J, Todorović N, Krstonošić V, Ristić I, Kovačević Z, Vuković M, Lalić-Popović M. Liquid- and Semisolid-Filled Hard Gelatin Capsules Containing Alpha-Lipoic Acid as a Suitable Dosage Form for Compounding Medicines and Dietary Supplements. Pharmaceutics 2024; 16:892. [PMID: 39065589 PMCID: PMC11279521 DOI: 10.3390/pharmaceutics16070892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 06/29/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
Liquid-filled hard gelatin capsules may have pertinent advantages both for therapeutic effect and extemporaneous preparations of medicines. Alpha lipoic acid is a substance used in medicines and dietary supplements and there is a need for creating an appropriate formulation which would be suitable for each individual patient or consumer. Based on its biopharmaceutical and physical chemical characteristics, eight different capsule formulations were designed and characterized. Silicon dioxide was added to form a semisolid content and prevent leakage. The formulation filled with alpha lipoic acid solution in polyethylene glycol 400 showed the best performance. Although the addition of silicon dioxide to the formulation with polyethylene glycol 400 led to a change in both flow character and viscosity, the release rate did not show a statistically significant decrease (more than 85% of content was released after 5 min testing). Applied technique is a simple and an appropriate approach for compounding and could be used for other substances with similar properties.
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Affiliation(s)
- Jelena Jovičić-Bata
- Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia; (J.J.-B.); (V.K.); (M.V.); (M.L.-P.)
| | - Nemanja Todorović
- Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia; (J.J.-B.); (V.K.); (M.V.); (M.L.-P.)
| | - Veljko Krstonošić
- Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia; (J.J.-B.); (V.K.); (M.V.); (M.L.-P.)
| | - Ivan Ristić
- Faculty of Technology Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Zorana Kovačević
- Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Milana Vuković
- Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia; (J.J.-B.); (V.K.); (M.V.); (M.L.-P.)
| | - Mladena Lalić-Popović
- Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia; (J.J.-B.); (V.K.); (M.V.); (M.L.-P.)
- Centre for Medical and Pharmaceutical Investigations and Quality Control (CEMPhIC), Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia
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Bellini C, Mancin F, Papini E, Tavano R. Nanotechnological Approaches to Enhance the Potential of α-Lipoic Acid for Application in the Clinic. Antioxidants (Basel) 2024; 13:706. [PMID: 38929145 PMCID: PMC11201002 DOI: 10.3390/antiox13060706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 05/30/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
α-lipoic acid is a naturally occurring compound with potent antioxidant properties that helps protect cells and tissues from oxidative stress. Its incorporation into nanoplatforms can affect factors like bioavailability, stability, reactivity, and targeted delivery. Nanoformulations of α-lipoic acid can significantly enhance its solubility and absorption, making it more bioavailable. While α-lipoic acid can be prone to degradation in its free form, encapsulation within nanoparticles ensures its stability over time, and its release in a controlled and sustained manner to the targeted tissues and cells. In addition, α-lipoic acid can be combined with other compounds, such as other antioxidants, drugs, or nanomaterials, to create synergistic effects that enhance their overall therapeutic benefits or hinder their potential cytotoxicity. This review outlines the advantages and drawbacks associated with the use of α-lipoic acid, as well as various nanotechnological approaches employed to enhance its therapeutic effectiveness, whether alone or in combination with other bioactive agents. Furthermore, it describes the engineering of α-lipoic acid to produce poly(α-lipoic acid) nanoparticles, which hold promise as an effective drug delivery system.
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Affiliation(s)
- Chiara Bellini
- Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/b, 35121 Padova, Italy; (C.B.); (E.P.)
| | - Fabrizio Mancin
- Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35121 Padova, Italy;
| | - Emanuele Papini
- Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/b, 35121 Padova, Italy; (C.B.); (E.P.)
| | - Regina Tavano
- Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/b, 35121 Padova, Italy; (C.B.); (E.P.)
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Nguyen M, Aulick S, Kennedy C. Effectiveness of Vitamin D and Alpha-Lipoic Acid in COVID-19 Infection: A Literature Review. Cureus 2024; 16:e59153. [PMID: 38803740 PMCID: PMC11129797 DOI: 10.7759/cureus.59153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2024] [Indexed: 05/29/2024] Open
Abstract
Over three years since the World Health Organization (WHO) declared COVID-19 a pandemic, it is still a global burden. Vaccines against COVID-19, caused by SARS-CoV-2, are available and effective for preventing disease. However, their protective effects are not 100%. Currently, the U.S. Food and Drug Administration (FDA) has only approved a limited number of inpatient treatments for COVID-19, such as remdesivir, baricitinib, and tocilizumab. These medications have indications and contraindications applicable to a select patient population. Finding additional effective therapies that are widely available with limited risk could be vital in optimizing treatment strategies for this viral illness. Some vitamins and supplements have been identified as potential options for managing COVID-19. Vitamin D (VD) deficiency has been associated with respiratory tract infections. Moreover, alpha-lipoic acid (ALA) is a powerful antioxidant and helps reduce inflammatory responses in many pathologic conditions. This review aims to analyze the current evidence regarding the effectiveness of VD and alpha-lipoic acid in COVID-19 infection in both outpatient and hospitalized patients. Relevant randomized controlled trials (RCTs) were identified via the PubMed database from January 1, 2021, to December 31, 2023. Inclusion criteria were as follows: the study design was a randomized controlled trial (RCT), the usage of a constant dose during the intervention period without any additional boluses, and a research ethics committee approved it. Exclusion criteria included a lack of an outcome or apparent intervention, additional boluses, or a single-dose regimen in all the interventional groups. There were 11 studies with a total sample size of 35,717 patients that met the criteria for this review. A total of 10 RCTs examined the efficacy of VD, and one RCT that reviewed the efficacy of ALA was identified. All of the articles investigated the use of VD or ALA during the treatment of COVID-19. The endpoints of each study varied, including length of stay in hospital, viral load, SARS-CoV-2 infection rate, mechanical ventilation, inflammatory markers, clinical symptoms, Sequential Organ Failure Assessment (SOFA) score, and mortality. In 8/10 VD supplementation trials, significant differences were identified between the interventional and placebo groups in the aforementioned parameters. In 2/10 VD supplementation trials, no significant differences were identified. The ALA supplementation RCT found no differences between the interventional and placebo groups in the SOFA score and 30-day all-cause mortality rate. The current literature suggests that VD can potentially reduce the SARS-CoV-2 infection rate, oxygen requirements, inflammatory markers, clinical symptoms, and mortality. Regarding ALA, although there was a suggestion of benefit, it was not statistically significant. Common limitations among the different studies included relatively small sample sizes, different geographical patient locations among studies, and differences in dosages. Trials investigating the effects of higher doses of VD supplementation on SARS-CoV-2 infection should be conducted. More research is needed to define best practices and optimal dosing protocols for the use of VD in COVID-19.
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Affiliation(s)
- Martin Nguyen
- Clinical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, USA
| | - Samuel Aulick
- Clinical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, USA
| | - Christopher Kennedy
- Clinical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, USA
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Yan Z, Wan J, Liu J, Yao B, Lu Y, Guo Z, Li Y. α-lipoic acid ameliorates hepatotoxicity induced by chronic ammonia toxicity in crucian carp (Carassius auratus gibelio) by alleviating oxidative stress, inflammation and inhibiting ERS pathway. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 266:115533. [PMID: 37806127 DOI: 10.1016/j.ecoenv.2023.115533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/23/2023] [Accepted: 09/26/2023] [Indexed: 10/10/2023]
Abstract
High environment ammonia (HEA) poses a deadly threat to aquatic animals and indirectly impacts human healthy life, while nutritional regulation can alleviate chronic ammonia toxicity. α-lipoic acid exhibits antioxidative effects in both aqueous and lipid environments, mitigating cellular and tissue damage caused by oxidative stress by aiding in the neutralization of free radicals (reactive oxygen species). Hence, investigating its potential as an effective antioxidant and its protective mechanisms against chronic ammonia stress in crucian carp is highly valuable. Experimental fish (initial weight 20.47 ± 1.68 g) were fed diets supplemented with or without 0.1% α-lipoic acid followed by a chronic ammonia exposure (10 mg/L) for 42 days. The results revealed that chronic ammonia stress affected growth (weight gain rate, specific growth rate, and feed conversion rate), leading to oxidative stress (decreased the activities of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase; decreased total antioxidant capacity), increased lipid peroxidation (accumulation of malondialdehyde), immune suppression (decreased contents of nonspecific immune enzymes AKP and ACP, 50% hemolytic complement, and decrease of immunoglobulin M), impaired ammonia metabolism (reduced contents of Glu, GS, GSH, and Gln), imbalance of expression of induced antioxidant-related genes (downregulation of Cu/Zu SOD, CAT, Nrf2, and HO-1; upregulation of GST and Keap1), induction of pro-apoptotic molecules (transcription of BAX, Caspase3, and Caspase9), downregulation of anti-apoptotic gene Bcl-2 expression, and induction of endoplasmic reticulum stress (upregulation of IRE1, PERK, and ATF6 expression). The results suggested that the supplementation of α-lipoic acid could effectively induce humoral immunity, alleviate oxidative stress injury and endoplasmic reticulum stress, and ultimately alleviate liver injury induced by ammonia poisoning (50-60% reduction). This provides theoretical basis for revealing the toxicity of long-term ammonia stress and provides new insights into the anti-ammonia toxicity mechanism of α-lipoic acid.
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Affiliation(s)
- Zihao Yan
- College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Jiwu Wan
- Jilin Provincial Aquatic Technology Extension Center, Changchun 130118, China
| | - Jia Liu
- College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Baolan Yao
- College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Yuqian Lu
- College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Zhengyao Guo
- College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China
| | - Yuehong Li
- College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.
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Das A, Pathak MP, Pathak K, Saikia R, Gogoi U. Herbal medicine for the treatment of obesity-associated asthma: a comprehensive review. Front Pharmacol 2023; 14:1186060. [PMID: 37251328 PMCID: PMC10213975 DOI: 10.3389/fphar.2023.1186060] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 04/25/2023] [Indexed: 05/31/2023] Open
Abstract
Obesity is fast growing as a global pandemic and is associated with numerous comorbidities like cardiovascular disease, hypertension, diabetes, gastroesophageal reflux disease, sleep disorders, nephropathy, neuropathy, as well as asthma. Studies stated that obese asthmatic subjects suffer from an increased risk of asthma, and encounter severe symptoms due to a number of pathophysiology. It is very vital to understand the copious relationship between obesity and asthma, however, a clear and pinpoint pathogenesis underlying the association between obesity and asthma is scarce. There is a plethora of obesity-asthma etiologies reported viz., increased circulating pro-inflammatory adipokines like leptin, resistin, and decreased anti-inflammatory adipokines like adiponectin, depletion of ROS controller Nrf2/HO-1 axis, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) associated macrophage polarization, hypertrophy of WAT, activation of Notch signaling pathway, and dysregulated melanocortin pathway reported, however, there is a very limited number of reports that interrelates these pathophysiologies. Due to the underlying complex pathophysiologies exaggerated by obese conditions, obese asthmatics respond poorly to anti-asthmatic drugs. The poor response towards anti-asthmatic drugs may be due to the anti-asthmatics approach only that ignores the anti-obesity target. So, aiming only at the conventional anti-asthmatic targets in obese-asthmatics may prove to be futile until and unless treatment is directed towards ameliorating obesity pathogenesis for a holistic approach towards amelioration of obesity-associated asthma. Herbal medicines for obesity as well as obesity-associated comorbidities are fast becoming safer and more effective alternatives to conventional drugs due to their multitargeted approach with fewer adverse effects. Although, herbal medicines are widely used for obesity-associated comorbidities, however, a limited number of herbal medicines have been scientifically validated and reported against obesity-associated asthma. Notable among them are quercetin, curcumin, geraniol, resveratrol, β-Caryophyllene, celastrol, tomatidine to name a few. In view of this, there is a dire need for a comprehensive review that may summarize the role of bioactive phytoconstituents from different sources like plants, marine as well as essential oils in terms of their therapeutic mechanisms. So, this review aims to critically discuss the therapeutic role of herbal medicine in the form of bioactive phytoconstituents against obesity-associated asthma available in the scientific literature to date.
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Affiliation(s)
- Aparoop Das
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Manash Pratim Pathak
- Faculty of Pharmaceutical Science, Assam Down Town University, Guwahati, Assam, India
| | - Kalyani Pathak
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Riya Saikia
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
| | - Urvashee Gogoi
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India
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11
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Abstract
Respiratory diseases, including lung cancer, pulmonary fibrosis, asthma, and the recently emerging fatal coronavirus disease-19 (COVID-19), are the leading causes of illness and death worldwide. The increasing incidence and mortality rates have attracted much attention to the prevention and treatment of these conditions. Lipoic acid (LA), a naturally occurring organosulfur compound, is not only essential for mitochondrial aerobic metabolism but also shows therapeutic potential via certain pharmacological effects (e.g., antioxidative and anti-inflammatory effects). In recent years, accumulating evidence (animal experiments and in vitro studies) has suggested a role of LA in ameliorating many respiratory diseases (e.g., lung cancer, fibrosis, asthma, acute lung injury and smoking-induced lung injury). Therefore, this review will provide an overview of the present investigational evidence on the therapeutic effect of LA against respiratory diseases in vitro and in vivo. We also summarize the corresponding mechanisms of action to inspire further basic studies and clinical trials to confirm the health benefits of LA in the context of respiratory diseases.
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Key Words
- lipoic acid
- respiratory diseases
- antioxidation
- anti-inflammatory effects
- mechanism of action
- akt, protein kinase b;
- aif, apoptosis-inducing factor;
- ampk, adenosine monophosphate-activated protein kinase;
- α-sma, alpha-smooth muscle actin;
- bcl-2, b-cell lymphoma 2;
- cox-2, cyclooxygenase-2;
- dna, deoxyribonucleic acid;
- er, endoplasmic reticulum;
- erk, extracellular-regulated kinase;
- egfr, epidermal growth factor receptor;
- gr, glutathione reductase;
- gpx, glutathione peroxidase;
- grb2, growth factor receptor-bound protein 2;
- gsh, reduced glutathione;
- gssg, oxidized glutathione;
- hif, hypoxia-inducible factor;
- ho-1, heme oxygenase 1;
- keap-1, kelch-like ech-associated protein 1;
- ig-e, immunoglobulin e;
- il, interleukin
- oct-4, octamer-binding transcription factor 4;
- parp-1, poly (adp-ribose) polymerase-1;
- pdk1, phosphoinositide-dependent kinase-1;
- pdh, pyruvate dehydrogenase;
- pi3k, phosphoinositide 3-kinase;
- pge2, prostaglandin e2;
- pgc1α, peroxisome proliferator-activated receptor‑γ co-activator 1α;
- p70s6k, p70 ribosomal protein s6 kinase;
- fak, focal adhesion kinase;
- sod, superoxide dismutase;
- mapk, mitogen-activated protein kinase;
- mtor, mammalian target of rapamycin;
- nf-κb, nuclear factor-kappa b;
- no, nitric oxide;
- nox-4, nicotinamide adenine dinucleotide phosphate (nadph) oxidase-4;
- nqo1, nadph quinone oxidoreductase 1;
- tnf-α, tumor necrosis factor-α;
- tgf-β1, transforming growth factor beta-1;
- vegf, vascular endothelial growth factor;
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12
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Basile GA, Iannuzzo F, Xerra F, Genovese G, Pandolfo G, Cedro C, Muscatello MRA, Bruno A. Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:2358. [PMID: 36767724 PMCID: PMC9916195 DOI: 10.3390/ijerph20032358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Memory disorders are common among elder people, and nonclinical cognitive decline is commonly experienced with age. Preclinical investigations have explored the possible role of alpha-lipoic acid (ALA), a known antioxidant compound abundant in vegetables and animal tissues, in reducing oxidative stress in the aging brain and preventing cognitive decline. However, clinical evidence is limited, and the few existing results are contrasting. In addition, while most of the existing trials have been focused on the effects of ALA administration in Alzheimer's disease (AD) or other types of dementia, studies evaluating its effects on nonclinical elder population are still missing. METHODS In the present open-label, pilot study, fifteen elder patients (mean age: 84.5 ± 5.77) received ALA at a daily dose of 600 mg/day for 12 weeks. General cognitive function, executive function, and mood symptom assessment were carried out at baseline and at the endpoint. RESULTS Overall, ALA administration was generally well-tolerated (only one dropout due to gastrointestinal side effects). However, no statistically significant effects either on cognitive function, executive function, or mood were found. CONCLUSIONS Despite several limitations, our study found no evidence of positive effects on cognition and mood after ALA administration in elder people without the diagnosis of AD or cognitive impairment. Further clinical trials are needed to better investigate ALA effectiveness on cognition and mood in elder subjects.
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Affiliation(s)
- Gianpaolo Antonio Basile
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Fiammetta Iannuzzo
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Francesco Xerra
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Giovanni Genovese
- Psychiatry Unit, Polyclinic Hospital University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Gianluca Pandolfo
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
- Psychiatry Unit, Polyclinic Hospital University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Clemente Cedro
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
- Psychiatry Unit, Polyclinic Hospital University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Maria Rosaria Anna Muscatello
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
- Psychiatry Unit, Polyclinic Hospital University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
| | - Antonio Bruno
- Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
- Psychiatry Unit, Polyclinic Hospital University of Messina, Via Consolare Valeria 1, Contesse, 98125 Messina, Italy
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13
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Tripathi AK, Ray AK, Mishra SK, Bishen SM, Mishra H, Khurana A. Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention. REVISTA BRASILEIRA DE FARMACOGNOSIA : ORGAO OFICIAL DA SOCIEDADE BRASILEIRA DE FARMACOGNOSIA 2023; 33:272-287. [PMID: 36778891 PMCID: PMC9904877 DOI: 10.1007/s43450-023-00370-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 01/25/2023] [Indexed: 02/10/2023]
Abstract
Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s43450-023-00370-1.
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Affiliation(s)
- Amit Kumar Tripathi
- School of Basic and Applied Science, Galgotias University, Gautam Buddha Nagar, UP Noida, India
- Molecular Biology Unit, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005 India
| | - Anup Kumar Ray
- Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sahibzada Ajit Singh Nagar, Punjab, India
| | - Sunil Kumar Mishra
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005 India
| | - Siddharth Mall Bishen
- Department of Physics, Banaras Hindu University, Mahila Maha Vidyalaya, Varanasi, India
| | - Hirdyesh Mishra
- Department of Physics, Banaras Hindu University, Mahila Maha Vidyalaya, Varanasi, India
| | - Aman Khurana
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005 India
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14
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Espíndola KMM, Varela ELP, de Albuquerque RDFV, Figueiredo RA, dos Santos SM, Malcher NS, da S. Seabra PS, Fonseca ADN, de Azevedo Sousa KM, de Oliveira SBB, Carneiro ADS, Coleman MD, Monteiro MC. Alpha-Lipoic Acid and Its Enantiomers Prevent Methemoglobin Formation and DNA Damage Induced by Dapsone Hydroxylamine: Molecular Mechanism and Antioxidant Action. Int J Mol Sci 2022; 24:ijms24010057. [PMID: 36613503 PMCID: PMC9820452 DOI: 10.3390/ijms24010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/14/2022] [Accepted: 10/23/2022] [Indexed: 12/24/2022] Open
Abstract
Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.
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Affiliation(s)
- Kaio Murilo Monteiro Espíndola
- Postgraduate Program in Pharmacology and Biochemistry, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Everton Luiz Pompeu Varela
- Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | | | - Rosiane Araújo Figueiredo
- Postgraduate Program in Pharmacology and Biochemistry, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Sávio Monteiro dos Santos
- Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Nívea Silva Malcher
- Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Pamela Suelen da S. Seabra
- Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Andréia do Nascimento Fonseca
- Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Karla Marcely de Azevedo Sousa
- Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Susan Beatriz Batista de Oliveira
- Central Laboratory of the State of Pará-CLSP, Belém 66823-010, PA, Brazil
- Postgraduate Program in Neuroscience and Cell Biology, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Agnaldo da Silva Carneiro
- Postgraduate Program in Medicinal Chemistry and Molecular Modeling, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
| | - Michael D. Coleman
- College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
| | - Marta Chagas Monteiro
- Postgraduate Program in Pharmacology and Biochemistry, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
- Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
- Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Pará/UFPA, Belém 66075-110, PA, Brazil
- Correspondence:
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15
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Liao C, Wang X, Zhou X, Wang D, Zhang Z, Liu Y, Wu X, Chen Y, Tan Y, Dai X, Jing P, Pang J, Xiao X, Liu J, Liao X, Zhang S. Dietary Antioxidant-Constructed Nanodrugs Can High-Efficiently Kill Cancer Cells while Protecting Noncancer Cells. ACS APPLIED MATERIALS & INTERFACES 2022; 14:49508-49520. [PMID: 36315104 DOI: 10.1021/acsami.2c12043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Despite great advances, the development of cancer drugs that can efficiently kill cancer cells while protecting noncancer cells has not been achieved. By using only dietary antioxidants vitamin C (VC) and (R)-(+)-lipoic acid (LA), we herein develop a nanodrug VC@cLAV featuring the above function. After entering cells, cLAV dissociates into LA and DHLA (dihydrolipoic acid, reduced form of LA) and releases VC and DHA (dehydroascorbate, oxidized form of VC). In cancer cells, the two redox pairs recycle each other and dramatically promote the intracellular reactive oxygen species production to kill cancer cells at low doses comparable to cytotoxic drugs. Oppositely in noncancer cells, the LA/DHLA and VC/DHA pairs exert anti-oxidant action to actively protect the organism by preventing the normal cells from oxidative stress and repairing cells suffering from oxidative stress. When compared with the first-line cytotoxic drug, VC@cLAV displayed superior therapeutic outcomes yet without side effects in diverse tumor models including patient-derived xenograft (PDX). This drug with efficient cancer cell killing and noncancer cell protection represents a new cancer therapy.
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Affiliation(s)
- Chunyan Liao
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Xiang Wang
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu610041, China
| | - Xueying Zhou
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Dequan Wang
- Chengdu Seventh People's Hospital and Chengdu Cancer Hospital, 12 Middle Street, Chengdu610041, China
| | - Ziyin Zhang
- Chengdu Seventh People's Hospital and Chengdu Cancer Hospital, 12 Middle Street, Chengdu610041, China
| | - Yan Liu
- Center of Growth, Metabolism and Aging, School of Life Sciences, Sichuan University, Chengdu, Sichuan610065China
| | - Xiao Wu
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Ying Chen
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
- Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang, Guizhou550025, China
| | - Yifeng Tan
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Xin Dai
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
- Zunyi Medical and Pharmaceutical College, Pingan Road, Xinpu District, Zunyi56300, China
| | - Pei Jing
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
- Department of Pharmacy of the Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou646000, China
| | - Jie Pang
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Xiao Xiao
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Jie Liu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu610041, China
| | - Xiaoming Liao
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
| | - Shiyong Zhang
- College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu610064, China
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16
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Pisoschi AM, Iordache F, Stanca L, Gajaila I, Ghimpeteanu OM, Geicu OI, Bilteanu L, Serban AI. Antioxidant, Anti-inflammatory, and Immunomodulatory Roles of Nonvitamin Antioxidants in Anti-SARS-CoV-2 Therapy. J Med Chem 2022; 65:12562-12593. [PMID: 36136726 PMCID: PMC9514372 DOI: 10.1021/acs.jmedchem.2c01134] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Indexed: 11/28/2022]
Abstract
Viral pathologies encompass activation of pro-oxidative pathways and inflammatory burst. Alleviating overproduction of reactive oxygen species and cytokine storm in COVID-19 is essential to counteract the immunogenic damage in endothelium and alveolar membranes. Antioxidants alleviate oxidative stress, cytokine storm, hyperinflammation, and diminish the risk of organ failure. Direct antiviral roles imply: impact on viral spike protein, interference with the ACE2 receptor, inhibition of dipeptidyl peptidase 4, transmembrane protease serine 2 or furin, and impact on of helicase, papain-like protease, 3-chyomotrypsin like protease, and RNA-dependent RNA polymerase. Prooxidative environment favors conformational changes in the receptor binding domain, promoting the affinity of the spike protein for the host receptor. Viral pathologies imply a vicious cycle, oxidative stress promoting inflammatory responses, and vice versa. The same was noticed with respect to the relationship antioxidant impairment-viral replication. Timing, dosage, pro-oxidative activities, mutual influences, and interference with other antioxidants should be carefully regarded. Deficiency is linked to illness severity.
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Affiliation(s)
- Aurelia Magdalena Pisoschi
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Florin Iordache
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Loredana Stanca
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Iuliana Gajaila
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Oana Margarita Ghimpeteanu
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
| | - Ovidiu Ionut Geicu
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
- Faculty of Biology, Department Biochemistry and
Molecular Biology, University of Bucharest, 91-95 Splaiul
Independentei, 050095Bucharest, Romania
| | - Liviu Bilteanu
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
- Molecular Nanotechnology Laboratory,
National Institute for Research and Development in
Microtechnologies, 126A Erou Iancu Nicolae Street, 077190Bucharest,
Romania
| | - Andreea Iren Serban
- Faculty of Veterinary Medicine, Department Preclinical
Sciences, University of Agronomic Sciences and Veterinary Medicine of
Bucharest, 105 Splaiul Independentei, 050097Bucharest,
Romania
- Faculty of Biology, Department Biochemistry and
Molecular Biology, University of Bucharest, 91-95 Splaiul
Independentei, 050095Bucharest, Romania
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17
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Dugbartey GJ, Alornyo KK, Adams I, Atule S, Obeng-Kyeremeh R, Amoah D, Adjei S. Targeting hepatic sulfane sulfur/hydrogen sulfide signaling pathway with α-lipoic acid to prevent diabetes-induced liver injury via upregulating hepatic CSE/3-MST expression. Diabetol Metab Syndr 2022; 14:148. [PMID: 36229864 PMCID: PMC9558364 DOI: 10.1186/s13098-022-00921-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 10/05/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Diabetes-induced liver injury is a complication of diabetes mellitus of which there are no approved drugs for effective treatment or prevention. This study investigates possible hepatoprotective effect of alpha-lipoic acid (ALA), and sulfane sulfur/hydrogen sulfide pathway as a novel protective mechanism in a rat model of type 2 diabetes-induced liver injury. METHODS Thirty Sprague-Dawley rats underwent fasting for 12 h after which fasting blood glucose was measured and rats were randomly assigned to diabetic and non-diabetic groups. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). Diabetic rats were treated daily with ALA (60 mg/kg/day p.o.) or 40 mg/kg/day DL-propargylglycine (PPG, an inhibitor of endogenous hydrogen sulfide production) for 6 weeks and then sacrificed. Liver, pancreas and blood samples were collected for analysis. Untreated T2DM rats received distilled water. RESULTS Hypoinsulinemia, hyperglycemia, hepatomegaly and reduced hepatic glycogen content were observed in untreated T2DM rats compared to healthy control group (p < 0.001). Also, the pancreas of untreated T2DM rats showed severely damaged pancreatic islets while liver damage was characterized by markedly increased hepatocellular vacuolation, sinusoidal enlargement, abnormal intrahepatic lipid accumulation, severe transaminitis, hyperbilirubinemia, and impaired hepatic antioxidant status and inflammation compared to healthy control rats (p < 0.01). While pharmacological inhibition of hepatic sulfane sulfur/hydrogen sulfide with PPG administration aggravated these pathological changes (p < 0.05), ALA strongly prevented these changes. ALA also significantly increased hepatic expression of hydrogen sulfide-producing enzymes (cystathionine γ-lyase and 3-mecaptopyruvate sulfurtransferase) as well as hepatic sulfane sulfur and hydrogen sulfide levels compared to all groups (p < 0.01). CONCLUSIONS To the best of our knowledge, this is the first experimental evidence showing that ALA prevents diabetes-induced liver injury by activating hepatic sulfane sulfur/hydrogen sulfide pathway via upregulation of hepatic cystathionine γ-lyase and 3-mecaptopyruvate sulfurtransferase expressions. Therefore, ALA could serve as a novel pharmacological agent for the treatment and prevention of diabetes-induced liver injury, with hepatic sulfane sulfur/hydrogen sulfide as a novel therapeutic target.
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Affiliation(s)
- George J Dugbartey
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
| | - Karl K Alornyo
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Ismaila Adams
- Department of Medical Pharmacology, University of Ghana Medical School, Korle-Bu, Accra, Ghana
| | - Stephen Atule
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Richard Obeng-Kyeremeh
- Department of Animal Experimentation, College of Health Sciences, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana
| | - Daniel Amoah
- Department of Animal Experimentation, College of Health Sciences, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana
| | - Samuel Adjei
- Department of Animal Experimentation, College of Health Sciences, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana
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Ceylanlı D, Şehirli AÖ, Gençosman S, Teralı K, Şah H, Gülmez N, Sayıner S. Protective Effects of Alpha-Lipoic Acid against 5-Fluorouracil-Induced Gastrointestinal Mucositis in Rats. Antioxidants (Basel) 2022; 11:1930. [PMID: 36290656 PMCID: PMC9598092 DOI: 10.3390/antiox11101930] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/22/2022] [Accepted: 09/26/2022] [Indexed: 03/23/2024] Open
Abstract
Alpha-lipoic acid (ALA) is extensively utilized in multivitamin formulas and anti-aging products. The purpose of this study was to investigate the potential protective benefits of ALA on 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats. Tissues from the stomach, small intestine, and large intestine were excised, and blood sera were obtained to identify biochemical indices such as TNF-α, IL-1β, MDA, GPx, SOD, MMP-1, -2, -8, and TIMP-1. A histopathological study was also performed. The results revealed mucositis-elevated TNF-, IL-1, MDA, MMP-1, -2, -8, and TIMP-1 levels in both tissues and sera, and these values dropped dramatically following ALA treatment. Reduced SOD and GPx activities in mucositis groups were reversed in ALA-treated groups. The damage produced by mucositis in the stomach and small intestine regressed in the ALA-treated group, according to histopathological evaluation. Consequently, the implementation of ALA supplementation in 5-FU therapy may act as a protective intervention for cancer patients with gastrointestinal mucositis. In light of the findings, ALA, a food-derived antioxidant with pleiotropic properties, may be an effective treatment for 5-FU-induced gastrointestinal mucositus, and prevent oxidative stress, inflammation, and tissue damage in cancer patients receiving 5-FU therapy.
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Affiliation(s)
- Deniz Ceylanlı
- Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, Turkey
| | - Ahmet Özer Şehirli
- Department of Pharmacology, Faculty of Dentistry, Near East University, 99138 Nicosia, North Cyprus, Turkey
| | - Sevgi Gençosman
- Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, Turkey
| | - Kerem Teralı
- Department of Medical Biochemistry, Faculty of Medicine, Cyprus International University, 99258 Nicosia, Northern Cyprus, Turkey
| | - Hüseyin Şah
- Department of Histology and Embryology, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, Turkey
| | - Nurhayat Gülmez
- Department of Histology and Embryology, Faculty of Veterinary Medicine, Siirt University, 56100 Siirt, Turkey
| | - Serkan Sayıner
- Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, Turkey
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Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome. Clin Exp Med 2022:10.1007/s10238-022-00871-8. [PMID: 35994177 PMCID: PMC9395797 DOI: 10.1007/s10238-022-00871-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 08/03/2022] [Indexed: 12/02/2022]
Abstract
Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms. The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001). To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.
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El-Mancy EM, Elsherbini DMA, Al-Serwi RH, El-Sherbiny M, Ahmed Shaker G, Abdel-Moneim AMH, Enan ET, Elsherbiny NM. α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis. TOXICS 2022; 10:toxics10080442. [PMID: 36006121 PMCID: PMC9416703 DOI: 10.3390/toxics10080442] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 02/01/2023]
Abstract
The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP < GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H&E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy.
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Affiliation(s)
- Eman M. El-Mancy
- Deanship of Common First Year, Jouf University, P.O. Box 2014, Sakaka 42421, Saudi Arabia;
- Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11511, Egypt
| | - Dalia Mahmoud Abdelmonem Elsherbini
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, P.O. Box 2014, Sakaka 42421, Saudi Arabia;
- Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Rasha Hamed Al-Serwi
- Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
- Correspondence: (M.E.-S.); (N.M.E.)
| | - Gehan Ahmed Shaker
- Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (G.A.S.); (A.-M.H.A.-M.)
| | - Abdel-Moneim Hafez Abdel-Moneim
- Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (G.A.S.); (A.-M.H.A.-M.)
- Department of Medical Physiology, Faculty of Medicine, Qassim University, Buraydah 51452, Saudi Arabia
| | - Eman T. Enan
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;
| | - Nehal M. Elsherbiny
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
- Correspondence: (M.E.-S.); (N.M.E.)
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Dugbartey GJ, Wonje QL, Alornyo KK, Adams I, Diaba DE. Alpha-lipoic acid treatment improves adverse cardiac remodelling in the diabetic heart - The role of cardiac hydrogen sulfide-synthesizing enzymes. Biochem Pharmacol 2022; 203:115179. [PMID: 35853498 DOI: 10.1016/j.bcp.2022.115179] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/26/2022] [Accepted: 07/12/2022] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Alpha-lipoic acid (ALA) is a licensed drug for the treatment of diabetic neuropathy. We recently reported that it also improves diabetic cardiomyopathy (DCM) in type 2 diabetes mellitus (T2DM). In this study, we present evidence supporting our hypothesis that the cardioprotective effect of ALA is via upregulation of cardiac hydrogen sulfide (H2S)-synthesizing enzymes. METHODS Following 12 h of overnight fasting, T2DM was induced in 23 out of 30 male Sprague-Dawley rats by intraperitoneal administration of nicotinamide (110 mg/kg) followed by streptozotocin (55 mg/kg) while the rest served as healthy control (HC). T2DM rats then received either oral administration of ALA (60 mg/kg/day; n = 7) or 40 mg/kg/day DL-propargylglycine (PAG, an endogenous H2S inhibitor; n = 7) intraperitoneally for 6 weeks after which all rats were sacrificed and samples collected for analysis. Untreated T2DM rats served as diabetic control (DCM; n = 9). RESULTS T2DM resulted in weight loss, islet destruction, reduced pancreatic β-cell function and hyperglycemia. Histologically, DCM rats showed significant myocardial damage evidenced by myocardial degeneration, cardiomyocyte vacuolation and apoptosis, cardiac fibrosis and inflammation, which positively correlated with elevated levels of cardiac damage markers compared to HC rats (p < 0.001). These pathological alterations worsened significantly in PAG-treated rats (p < 0.05). However, ALA treatment restored normoinsulemia, normoglycemia, prevented DCM, and improved lipid and antioxidant status. Mechanistically, ALA significantly upregulated the expression of cardiac H2S-synthesizing enzymes and increased plasma H2S concentration compared to DCM rats (p < 0.001). CONCLUSION ALA preserves myocardial integrity in T2DM likely by maintaining the expression of cardiac H2S-synthezing enzymes and increasing plasma H2S level.
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Affiliation(s)
- George J Dugbartey
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
| | - Quinsker L Wonje
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Karl K Alornyo
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Ismaila Adams
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Deborah E Diaba
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
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22
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Dugbartey GJ, Alornyo KK, N'guessan BB, Atule S, Mensah SD, Adjei S. Supplementation of conventional anti-diabetic therapy with alpha-lipoic acid prevents early development and progression of diabetic nephropathy. Biomed Pharmacother 2022; 149:112818. [PMID: 35286963 DOI: 10.1016/j.biopha.2022.112818] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/07/2022] [Accepted: 03/09/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Current pharmacological interventions only retard DN progression. Alpha-lipoic acid (ALA) is a potent antioxidant with beneficial effect in other diabetic complications. This study investigates whether ALA supplementation prevents early development and progression of DN. METHOD Fifty-eight male Sprague-Dawley rats were randomly assigned to healthy control and diabetic groups and subjected to overnight fasting. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). On day 3 after T2DM induction, diabetic rats received oral daily administration of ALA (60 mg/kg), gliclazide (15 mg/kg), ramipril (10 mg/kg) or drug combinations for 6 weeks. Untreated diabetic rats served as diabetic control. Blood, kidneys and pancreas were harvested for biochemical and histological analyses. RESULT Induction of T2DM resulted in hypoinsulinemia, hyperglycemia and renal pathology. ALA supplementation maintained β-cell function, normoinsulinemia and normoglycemia in diabetic rats, and prevented renal pathology (PAS, KIM-1, plasma creatinine, total protein, blood urea nitrogen, uric acid and urine albumin/creatinine ratio) and triglycerides level compared to diabetic control (p < 0.001). Additionally, ALA supplementation significantly prevented elevated serum and tissue malondialdehyde, collagen deposition, α-SMA expression, apoptosis and serum IL-1β and IL-6 levels while it markedly increased renal glutathione content and plasma HDL-C compared to diabetic control group (p < 0.001). CONCLUSION ALA supplementation prevents early development and progression of DN by exerting anti-hyperglycemic, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic effects. Our findings provide additional option for clinical treatment of DN in T2DM patients.
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Affiliation(s)
- George J Dugbartey
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
| | - Karl K Alornyo
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Benoit B N'guessan
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Stephen Atule
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Samuel D Mensah
- Department of Pathology, University of Ghana Dental School, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Samuel Adjei
- Department of Animal Experimentation, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
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Abdulghani M, Naser A. Estimation of pharmacokinetic parameters of alpha-lipoic acid in the chicks model. BAGHDAD JOURNAL OF BIOCHEMISTRY AND APPLIED BIOLOGICAL SCIENCES 2022. [DOI: 10.47419/bjbabs.v3i02.91] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Background and objective: Alpha-lipoic acid is a drug used to treat diabetic neuropathy, and it has other uses as a dietary supplement. The target of the study was to investigate the concentration of therapeutic doses of Alpha-lipoic acid in the blood plasma of broiler chicks to define the pharmacokinetic parameters.
Methods: A randomized controlled study was performed on thirty-five healthy broiler chicks of seven days old, chicks were injected into the peritoneum with a single dose of analgesic ED50 80mg /kg b.wt, following injection of the drug, blood samples were collected at 0.25, 0.5, 1, 2, 4, 24 h (five chicks per time) from the jugular vein. Then the blood plasma was obtained, the concentrations of Alpha-lipoic acid in blood plasma samples were determined utilizing UV Spectrometric Method, the pharmacokinetic parameters were determined by the PKSolver program. Time versus concentration curve for Alpha-lipoic acid was obtained from the program. The pharmacokinetic parameters were determined with non-compartmental models.
Results: The concentration of Alpha-lipoic acid in the blood plasma of chicks injected with Alpha lipoic at a dose (80 mg/kg) were 134.6±7.17, 178.5±4.10 ,192.4±7.83 ,158.5±11.05 ,147.1±10.16, 122.8±7.09 µg/ml at times 0.25, 0.5, 1, 2, 4, and 24 hours respectively. The maximum plasma concentration was 192.4µg/ml during a period of 1 hour of injection. The terminal elimination half-life was 65hours, the terminal phase elimination rate constant was 0.011 h-1 , the mean residence time was 94h, and the area under the curve from time 0 to infinity was 14960 µg.h/ml.
Conclusions: Our study concluded that the peak of the analgesic effect of alpha lipoic acid was one hour after treatment; furthermore, it is characterized by a long elimination half-life and a poor clearance from the chick’s body, which is reflected in the long effects of its pharmacological properties
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PATANO A, DI VENERE D, CECI S, BERATE P, CANDREA S, BABTAN AM, AZZOLLINI D, PIRAS F, CURATOLI L, CORRIERO A, VALENTE F, MAGGIORE ME, MANCINI A, GIOVANNIELLO D, NUCCI L, ELIA R, SIRBU A, FEURDEAN C, GALDERISI A, CARDARELLI F. Essential oils utility implications in symptomatic Burning Mouth Syndrome. BALNEO AND PRM RESEARCH JOURNAL 2021. [DOI: 10.12680/balneo.2021.466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Introduction. Burning mouth syndrome (BMS) is a clinical condition characterized by the presence of chronic pain in absence of clinically visible lesions of the oral mucosa. The etiology is uncertain and the therapeutic strategies still controversial. The objective of this prospective study is to analyze the efficacy of essential oils-based mouthwashes in the therapy of BMS.
Material and method. This study included 16 patients affected by BMS who were treated with essential oils-based mouthwashes and glucose solution on alternated days for 30 days. Symptomatology was evaluated after 15, 30 and 90 days.
Results and discussions. A the end of the treatment, most of the patients (67%) referred an improvement of symptoms up to complete remission in 90 days.
Conclusions. Based on this study, essential oils-based mouthwashes could represent a valid aid in the treatment of BMS. Further studies are necessary in order to identify effective and standardized therapeutic protocols.
Keywords: Burning Mouth Syndrome; oral rinse; essential oils; therapeutic strategies,
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Affiliation(s)
- Assunta PATANO
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Daniela DI VENERE
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Sabino CECI
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Pula BERATE
- Privat clinic, Allias Vure, Rruga, Tirane, Albania
| | - Sebastian CANDREA
- Department of Oral Rehabilitation, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
| | - Anida-Maria BABTAN
- Department of Oral Rehabilitation, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
| | - Daniela AZZOLLINI
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Fabio PIRAS
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Luigi CURATOLI
- Department Neurosciences & Sensory Organs & Musculoskeletal system. University of Bari “Aldo Moro”, Bari, Italy
| | - Alberto CORRIERO
- Unit of Anesthesia and Resuscitation, Department of Emergencies and Organ Transplantations, “Aldo Moro” University, Bari, Italy
| | - Francesco VALENTE
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Maria Elena MAGGIORE
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | - Antonio MANCINI
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
| | | | - Ludovica NUCCI
- Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Rossella ELIA
- Unit of Anesthesia and Resuscitation, Department of Emergencies and Organ Transplantations, “Aldo Moro” University, Bari, Italy
| | - Adina SIRBU
- Department of Oral Health, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
| | - Claudia FEURDEAN
- Department of Oral Rehabilitation, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
| | | | - Fillippo CARDARELLI
- Department of Interdisciplinary Medicine (D.I.M), University of Medicine “Aldo Moro”, Bari, Italy
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Joksimovic SL, Lamborn N, Jevtovic-Todorovic V, Todorovic SM. Alpha lipoic acid attenuates evoked and spontaneous pain following surgical skin incision in rats. Channels (Austin) 2021; 15:398-407. [PMID: 33843451 PMCID: PMC8043189 DOI: 10.1080/19336950.2021.1907058] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/15/2021] [Accepted: 03/15/2021] [Indexed: 01/19/2023] Open
Abstract
Our previous studies have implicated CaV3.2 isoform of T-type Ca2+ channels (T-channels) in the development of postsurgical pain. We have also previously established that different T-channel antagonists can alleviate in vivo postsurgical pain. Here we investigated the analgesic potential of another T-channel blocker and endogenous antioxidant molecule, α-lipoic acid (ALA), in a postsurgical pain model in rats. Our in vivo results suggest that single and repetitive intraperitoneal injections of ALA after surgery or preemptively, significantly reduced evoked mechanical hyperalgesia following surgical paw incision. Furthermore, repeated preemptive systemic injections of ALA effectively alleviated spontaneous postsurgical pain as determined by dynamic weight-bearing testing. We expect that our preclinical study may lead to further investigation of analgesic properties and mechanisms of analgesic action of ALA in patients undergoing surgery.
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Affiliation(s)
- Sonja Lj. Joksimovic
- Department of Anesthesiology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
| | - Nathan Lamborn
- Department of Anesthesiology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
| | - Vesna Jevtovic-Todorovic
- Department of Anesthesiology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
| | - Slobodan M. Todorovic
- Department of Anesthesiology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA
- Neuroscience Graduate Program, Graduate Program in Pharmacology, and Graduate Program in Biomedical Sciences, University of Colorado Denver, Anschutz Medical Campus and Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
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Effects of Lipoic Acid on Ischemia-Reperfusion Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5093216. [PMID: 34650663 PMCID: PMC8510805 DOI: 10.1155/2021/5093216] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 09/07/2021] [Accepted: 09/14/2021] [Indexed: 12/15/2022]
Abstract
Ischemia-reperfusion (I/R) injury often occurred in some pathologies and surgeries. I/R injury not only harmed to physiological functions of corresponding organ and tissue but also induced multiple tissue or organ dysfunctions (even these in distant locations). Although the reperfusion of blood attenuated I/R injury to a certain degree, the risk of secondary damages was difficult to be controlled and it even caused failures of these tissues and organs. Lipoic acid (LA), as an endogenous active substance and a functional agent in food, owns better safety and effects in our body (e.g., enhancing antioxidant activity, improving cognition and dementia, controlling weight, and preventing multiple sclerosis, diabetes complication, and cancer). The literature searching was conducted in PubMed, Embase, Cochrane Library, Web of Science, and SCOPUS from inception to 20 May 2021. It had showed that endogenous LA was exhausted in the process of I/R, which further aggravated I/R injury. Thus, supplements with LA timely (especially pretreatments) may be the prospective way to prevent I/R injury. Recently, studies had demonstrated that LA supplements significantly attenuated I/R injuries of many organs, though clinic investigations were short at present. Hence, it was urgent to summarize these progresses about the effects of LA on different I/R organs as well as the potential mechanisms, which would enlighten further investigations and prepare for clinic applications in the future.
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A Collaborative Integrative and Ayurvedic Approach to Cirrhosis in the setting of Autoantibody Negative Autoimmune Hepatitis. ADVANCES IN INTEGRATIVE MEDICINE 2021. [DOI: 10.1016/j.aimed.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Skorupa A, Michalkiewicz S, Jakubczyk M. Highly sensitive determination of α-lipoic acid in pharmaceuticals on a boron-doped diamond electrode. OPEN CHEM 2021. [DOI: 10.1515/chem-2021-0075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
A simple, highly sensitive, and selective differential pulse voltammetry method for the determination of α-lipoic acid (LA) in pharmaceutical preparations was developed and validated. The method is based on a quasi-reversible, diffusion-controlled, one-electron anodic oxidation of LA on a boron-doped diamond electrode (BDDE) in a McIlvaine (citrate-phosphate, C-PB) buffer solution at pH 3.0. For the first time, this environment was used for LA determination. A linear calibration curve was obtained within the concentration range 5.82 × 10−8 to 4.00 × 10−4 mol L−1 with a correlation coefficient of 0.9999. The limits of detection was estimated to be 1.94 × 10−8 mol L−1, which is one of the lowest values characteristic of voltammetric and chromatographic methods of LA determination. The proposed procedure is sensitive, accurate, and precise. Its utility was demonstrated in the determination of LA in pharmaceuticals without the need for its separation from the matrices. The results were comparable to those obtained by high performance liquid chromatography reference method and were in good accordance with the once declared by manufacturers. Thus, our method can be considered as an alternative to the dominant chromatographic determinations of α-LA in real samples.
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Affiliation(s)
- Agata Skorupa
- Institute of Chemistry, Jan Kochanowski University , 7G Uniwersytecka St. , 25-406 Kielce , Poland
| | - Slawomir Michalkiewicz
- Institute of Chemistry, Jan Kochanowski University , 7G Uniwersytecka St. , 25-406 Kielce , Poland
| | - Magdalena Jakubczyk
- Institute of Chemistry, Jan Kochanowski University , 7G Uniwersytecka St. , 25-406 Kielce , Poland
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Lim J, Ali S, Liao LS, Nguyen ES, Ortiz L, Reshel S, Luderer U. Antioxidant supplementation partially rescues accelerated ovarian follicle loss, but not oocyte quality, of glutathione-deficient mice†. Biol Reprod 2021; 102:1065-1079. [PMID: 31950131 DOI: 10.1093/biolre/ioaa009] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 12/16/2019] [Accepted: 01/13/2020] [Indexed: 12/31/2022] Open
Abstract
The tripeptide thiol antioxidant glutathione (GSH) has multiple physiological functions. Female mice lacking the modifier subunit of glutamate cysteine ligase (GCLM), the rate-limiting enzyme in GSH synthesis, have decreased GSH concentrations, ovarian oxidative stress, preimplantation embryonic mortality, and accelerated age-related decline in ovarian follicles. We hypothesized that supplementation with thiol antioxidants, N-acetyl cysteine (NAC), or α-lipoic acid (ALA) will rescue this phenotype. Gclm-/- and Gclm+/+ females received 0 or 80 mM NAC in drinking water from postnatal day (PND) 21-30; follicle growth was induced with equine chorionic gonadotropin (eCG) on PND 27, followed by an ovulatory dose of human CG and mating with a wild type male on PND 29 and zygote harvest 20 h after hCG. N-acetyl cysteine supplementation failed to rescue the low rate of second pronucleus formation in zygotes from Gclm-/- versus Gclm+/+ females. In the second study, Gclm-/- and Gclm+/+ females received diet containing 0, 150, or 600 mg/kg ALA beginning at weaning and were mated with wild type males from 8 to 20 weeks of age. α-Lipoic acid failed to rescue the decreased offspring production of Gclm-/- females. However, 150 mg/kg diet ALA partially rescued the accelerated decline in primordial follicles, as well as the increased recruitment of follicles into the growing pool and the increased percentages of follicles with γH2AX positive oocytes or granulosa cells of Gclm-/- females. We conclude that ovarian oxidative stress is the cause of accelerated primordial follicle decline, while GSH deficiency per se may be responsible for preimplantation embryonic mortality in Gclm-/- females.
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Affiliation(s)
- Jinhwan Lim
- Department of Medicine, University of California, Irvine, California, USA
| | - Samiha Ali
- Department of Medicine, University of California, Irvine, California, USA
| | - Lisa S Liao
- Department of Medicine, University of California, Irvine, California, USA
| | - Emily S Nguyen
- Department of Medicine, University of California, Irvine, California, USA
| | - Laura Ortiz
- Department of Medicine, University of California, Irvine, California, USA
| | - Samantha Reshel
- Department of Developmental and Cell Biology, University of California, Irvine, California, USA
| | - Ulrike Luderer
- Department of Medicine, University of California, Irvine, California, USA.,Department of Developmental and Cell Biology, University of California, Irvine, California, USA.,Program in Public Health, University of California, Irvine, California, USA
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Dragomanova S, Miteva S, Nicoletti F, Mangano K, Fagone P, Pricoco S, Staykov H, Tancheva L. Therapeutic Potential of Alpha-Lipoic Acid in Viral Infections, including COVID-19. Antioxidants (Basel) 2021; 10:1294. [PMID: 34439542 PMCID: PMC8389191 DOI: 10.3390/antiox10081294] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/10/2021] [Accepted: 08/13/2021] [Indexed: 12/20/2022] Open
Abstract
Oxidative stress (OS), resulting from a disrupted balance between reactive oxygen species (ROS) and protective antioxidants, is thought to play an important pathogenetic role in several diseases, including viral infections. Alpha-lipoic acid (LA) is one of the most-studied and used natural compounds, as it is endowed with a well-defined antioxidant and immunomodulatory profile. Owing to these properties, LA has been tested in several chronic immunoinflammatory conditions, such as diabetic neuropathy and metabolic syndrome. In addition, a pharmacological antiviral profile of LA is emerging, that has attracted attention on the possible use of this compound for the cotreatment of several viral infections. Here, we will review the emerging literature on the potential use of LA in viral infections, including COVID-19.
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Affiliation(s)
- Stela Dragomanova
- Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University, 9002 Varna, Bulgaria;
| | - Simona Miteva
- Department of Behavior Neurobiology, Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (S.M.); (L.T.)
| | - Ferdinando Nicoletti
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy; (K.M.); (P.F.); (S.P.)
| | - Katia Mangano
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy; (K.M.); (P.F.); (S.P.)
| | - Paolo Fagone
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy; (K.M.); (P.F.); (S.P.)
| | - Salvatore Pricoco
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy; (K.M.); (P.F.); (S.P.)
| | - Hristian Staykov
- Department of Pharmacology and toxicology, Medical University, Sofia, 2, Zdrave Str., 1431 Sofia, Bulgaria;
| | - Lyubka Tancheva
- Department of Behavior Neurobiology, Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (S.M.); (L.T.)
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Turck D, Castenmiller J, de Henauw S, Hirsch‐Ernst KI, Kearney J, Knutsen HK, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cappellani D, Ijzerman R, Van Loveren H, Titz A, Maciuk A. Scientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome. EFSA J 2021; 19:e06577. [PMID: 34122657 PMCID: PMC8173454 DOI: 10.2903/j.efsa.2021.6577] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the relationship between alpha-lipoic acid (ALA) and the risk of insulin autoimmune syndrome (IAS). The Panel was also asked to advise on the dose below which ALA added to foods is not expected to cause IAS. A review of all possible adverse effects associated with consumption of ALA was not requested. This mandate refers to the procedure under Article 8(2) of Regulation (EC) No 1925/2006 on addition of vitamins, minerals and certain other substances to foods. No pre-established rule exists for the evaluation of the safety of foods when classical toxicity tests cannot be used, e.g. for autoimmune diseases. Published scientific evidence was retrieved through comprehensive literature searches, particularly 49 case reports in which IAS developed following ALA consumption. In all cases, IAS resolved after a few weeks to months when ALA was discontinued. No publication linking the intake of ALA naturally occurring in foods to IAS was identified. The Panel concludes that the consumption of ALA added to foods, including food supplements, is likely to increase the risk of developing IAS in individuals with certain genetic polymorphisms, who cannot be readily identified without genetic testing. The plausible mechanism of such an effect has not yet been fully elucidated. The incidence of IAS in Europe is low and likely lower than in Japan where it has been estimated to be 0.017 per 100,000 inhabitants in 2017-2018. Considering the limited data available, the risk associated with the development of IAS following ALA consumption cannot be quantified precisely. An ALA dose below which IAS is not expected to occur is likely to vary between individuals and cannot be determined from the available data.
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Shi J, Chang X, Zou H, Gu J, Yuan Y, Liu X, Liu Z, Bian J. Protective Effects of α-Lipoic Acid and Chlorogenic Acid on Cadmium-Induced Liver Injury in Three-Yellow Chickens. Animals (Basel) 2021; 11:ani11061606. [PMID: 34072384 PMCID: PMC8228482 DOI: 10.3390/ani11061606] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Cadmium (Cd) exerts pernicious influences on global health. We evaluated the protective effects of α-lipoic acid (α-LA) or chlorogenic acid (CGA) and their combination on counteracting Cd toxicity in vivo in three-yellow chickens. Administration of Cd (50 mg/L) alone lowered the production performance and resulted in biochemical, histologic and enzyme changes within the liver consistent with hepatic injury induced by oxidative stress and apoptosis of hepatocytes. However, the above variations of the Cd group were partially or fully reversed by administration of either α-LA or CGA; their combination showed an even better effect in attenuating Cd-induced hepatotoxicity. This study provided a practical and feasible approach to rescuing Cd intoxication in animal production. Abstract Cadmium (Cd) is a type of noxious heavy metal that is distributed widely. It can severely injure the hepatocytes and cause liver dysfunction by inducing oxidative stress and mitochondrial damage. We evaluated the protective effects of α-lipoic acid (α-LA) or chlorogenic acid (CGA) and their combination on counteracting cadmium toxicity in vivo in three-yellow chickens. For three months, CdCl2 (50 mg/L) was administrated through their drinking water, α-LA (400 mg/kg) was added to feed and CGA (45 mg/kg) was employed by gavage. The administration of Cd led to variations in growth performance, biochemical markers (of the liver, kidney and heart), hematological parameters, liver histopathology (which suggested hepatic injury) and ultrastructure of hepatocytes. Some antioxidant enzymes and oxidative stress parameters showed significant differences in the Cd-exposure group when compared with the control group. The groups treated with Cd and administrated α-LA or CGA showed significant amelioration with inhibited mitochondrial pathway-induced apoptosis. Combining both drugs was the most effective in reducing Cd toxicity in the liver. In summary, the results demonstrated that α-LA and CGA may be beneficial in alleviating oxidative stress induced by oxygen free radicals and tissue injury resulting from Cd-triggered hepatotoxicity.
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Affiliation(s)
- Jiabin Shi
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Xiaocui Chang
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Hui Zou
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Jianhong Gu
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Yan Yuan
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Xuezhong Liu
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
| | - Zongping Liu
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
| | - Jianchun Bian
- College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; (J.S.); (X.C.); (H.Z.); (J.G.); (Y.Y.); (X.L.); (Z.L.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
- Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
- Correspondence: ; Tel.: +86-514-879-79042
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Banik S, Halder S, Sato H, Onoue S. Self-emulsifying drug delivery system of (R)-α-lipoic acid to improve its stability and oral absorption. Biopharm Drug Dispos 2021; 42:226-233. [PMID: 33843079 DOI: 10.1002/bdd.2277] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 03/02/2021] [Accepted: 03/04/2021] [Indexed: 02/03/2023]
Abstract
The present study was designed to develop a self-emulsifying drug delivery system (SEDDS) of (R)-α-lipoic acid (RLA) to improve the physicochemical and nutraceutical properties of RLA. RLA/SEDDS was prepared using medium-chain triglycerides, Tween 80, and polyethylene glycol 400 as oil, surfactant, and co-surfactant, respectively. The preferable composition of SEDDS was selected according to a pseudo-ternary phase diagram for improved emulsification properties, and its physicochemical and pharmacokinetic properties were evaluated. RLA/SEDDS showed the immediate formation of fine micelles with a mean droplet size of approximately 260 nm when introduced into aqueous media. In simulated gastric fluid, this system could significantly improve the dissolution behavior of RLA and prevent the degradation of RLA, possibly due to the encapsulation of RLA into the emulsion structure. Following the oral administration of RLA/SEDDS (10 mg RLA/kg) in rats, systemic exposure to RLA and dihydrolipoic acid (DHLA), a reduced form of RLA, increased by 7- and 3-fold, respectively. The improved dissolution and gastric stability of RLA could contribute to enhancing systemic exposure to RLA and DHLA after oral administration. From these findings, RLA/SEDDS might be an efficacious dosage option for improving the oral bioavailability as well as nutraceutical properties of RLA.
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Affiliation(s)
- Sujan Banik
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Shimul Halder
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Hideyuki Sato
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Satomi Onoue
- Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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Kim K, Kim J, Kim H, Sung GY. Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model. Int J Mol Sci 2021; 22:2160. [PMID: 33671528 PMCID: PMC7927099 DOI: 10.3390/ijms22042160] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/18/2021] [Accepted: 02/18/2021] [Indexed: 11/16/2022] Open
Abstract
Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.
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Affiliation(s)
- Kyunghee Kim
- Interdisciplinary Program of Nano-Medical Device Engineering, Graduate School, Hallym University, Chuncheon 24252, Korea; (K.K.); (J.K.); (H.K.)
- Integrative Materials Research Institute, Hallym University, Chuncheon 24252, Korea
| | - Jisue Kim
- Interdisciplinary Program of Nano-Medical Device Engineering, Graduate School, Hallym University, Chuncheon 24252, Korea; (K.K.); (J.K.); (H.K.)
- Integrative Materials Research Institute, Hallym University, Chuncheon 24252, Korea
| | - Hyoungseob Kim
- Interdisciplinary Program of Nano-Medical Device Engineering, Graduate School, Hallym University, Chuncheon 24252, Korea; (K.K.); (J.K.); (H.K.)
- Integrative Materials Research Institute, Hallym University, Chuncheon 24252, Korea
| | - Gun Yong Sung
- Interdisciplinary Program of Nano-Medical Device Engineering, Graduate School, Hallym University, Chuncheon 24252, Korea; (K.K.); (J.K.); (H.K.)
- Integrative Materials Research Institute, Hallym University, Chuncheon 24252, Korea
- Major in Materials Science and Engineering, School of Future Convergence, Hallym University, Chuncheon 24252, Korea
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Comparison between two preventive treatments for hyperketonaemia carried out pre-partum: effects on non-esterified fatty acids, β-hydroxybutyrate and some biochemical parameters during peripartum and early lactation. J DAIRY RES 2021; 88:38-44. [PMID: 33594962 DOI: 10.1017/s0022029921000108] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The objective of this study was to compare the effect of two different preventive protocols, on serum β-hydroxybutyrate (BHB) concentration and liver health indices pre-partum and during early-lactation in high-yielding Holstein dairy cows. One hundred cows were randomly divided into three groups: control group (CTRL, n = 20, without preventive treatment), second group (SUPP, n = 40 animals treated with a compound based on acetyl-methionine, inositol, cyanocobalamin, l-alanine, l-arginine, l-threonine, l-glutamic acid supplementation and α-lipoic acid) and third group (MON, n = 40 animals treated with monensin). Blood samples were collected from all cows at on 3 occasions pre-partum and 3 occasions post-partum. Body condition (BCS) score was evaluated and glucose, non-esterified fatty acids (NEFA), BHB, triglycerides, total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin, total proteins, globulins, albumin and urea concentrations were assessed. Two-way repeated measures analysis of variance was applied. Statistically significant differences among the three experimental groups were found in the values of all studied parameters (P < 0.05). Our results confirm the established beneficial effect of MON treatment in decreasing BHB levels and increasing glucose availability after calving. Serum biochemical analysis revealed the expected post-partum alterations attributable to adaptations that influenced the metabolism and liver function in CTRL, whereas these alterations were reduced or absent in SUPP and MON. Results from the present study suggest that both preventive protocols, but in particular SUPP, could positively affect selected indicators of energy metabolism reducing the risk of hyperketonaemia and increase of liver function in Holstein dairy cows, both pre- and post-partum.
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Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, Dureja H, Singh SK, Chellappan DK, Dua K, Pandi B, Saravanan M, Chuturgoon AA. Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies. ACS OMEGA 2021; 6:265-277. [PMID: 33458478 PMCID: PMC7807466 DOI: 10.1021/acsomega.0c04461] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 12/09/2020] [Indexed: 06/12/2023]
Abstract
In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
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Affiliation(s)
- Krishnan Anand
- Department
of Chemical Pathology, School of Pathology, Faculty of Health Sciences
and National Health Laboratory Service, University of the Free State, Bloemfontein 9300, South Africa
| | - Naeem Sheik Abdul
- Discipline
of Medical Biochemistry, School of Laboratory Medicine and Medical
Science, University of KwaZulu-Natal, Durban 4041, South Africa
| | - Terisha Ghazi
- Discipline
of Medical Biochemistry, School of Laboratory Medicine and Medical
Science, University of KwaZulu-Natal, Durban 4041, South Africa
| | - Muthusamy Ramesh
- Department
of Pharmaceutical Analysis, Omega College
of Pharmacy, Hyderabad 501 301, India
| | - Gaurav Gupta
- School
of Pharmacy, Suresh Gyan Vihar University, Jagatpura Mahal Road, Jaipur 302017, India
| | - Murtaza M. Tambuwala
- School
of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, United Kingdom
- School of
Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland BT52 1SA, United Kingdom
| | - Harish Dureja
- Department
of Pharmaceutical Sciences, Maharshi Dayanand
University, Rohtak 124001 Haryana, India
| | - Sachin Kumar Singh
- School
of Pharmaceutical Sciences, Lovely Professional
University, Phagwara, Punjab 144411, India
| | - Dinesh Kumar Chellappan
- School
of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
| | - Kamal Dua
- Discipline
of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales 2007, Australia
- Priority
Research Centre for Healthy Lungs, Hunter Medical Research
Institute (HMRI) & School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, New South Wales 2308, Australia
- School of
Pharmaceutical Sciences, Shoolini
University of Biotechnology and Management Sciences, Solan 173229, India
| | - Boomi Pandi
- Department of Bioinformatics, Alagappa
University, Karaikudi 630 003, India
| | - Muthupandian Saravanan
- Department
of Microbiology and Immunology, Division of Biomedical
Sciences, School of Medicine, College of Health Sciences, Mekelle University, Mekelle 1871, Ethiopia
| | - Anil Amichund Chuturgoon
- Discipline
of Medical Biochemistry, School of Laboratory Medicine and Medical
Science, University of KwaZulu-Natal, Durban 4041, South Africa
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Bottani E, Lamperti C, Prigione A, Tiranti V, Persico N, Brunetti D. Therapeutic Approaches to Treat Mitochondrial Diseases: "One-Size-Fits-All" and "Precision Medicine" Strategies. Pharmaceutics 2020; 12:E1083. [PMID: 33187380 PMCID: PMC7696526 DOI: 10.3390/pharmaceutics12111083] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/08/2020] [Accepted: 11/09/2020] [Indexed: 12/11/2022] Open
Abstract
Primary mitochondrial diseases (PMD) refer to a group of severe, often inherited genetic conditions due to mutations in the mitochondrial genome or in the nuclear genes encoding for proteins involved in oxidative phosphorylation (OXPHOS). The mutations hamper the last step of aerobic metabolism, affecting the primary source of cellular ATP synthesis. Mitochondrial diseases are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. The limited information of the natural history, the limitations of currently available preclinical models, coupled with the large variability of phenotypical presentations of PMD patients, have strongly penalized the development of effective therapies. However, new therapeutic strategies have been emerging, often with promising preclinical and clinical results. Here we review the state of the art on experimental treatments for mitochondrial diseases, presenting "one-size-fits-all" approaches and precision medicine strategies. Finally, we propose novel perspective therapeutic plans, either based on preclinical studies or currently used for other genetic or metabolic diseases that could be transferred to PMD.
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Affiliation(s)
- Emanuela Bottani
- Department of Diagnostics and Public Health, Section of Pharmacology, University of Verona, 37134 Verona, Italy
| | - Costanza Lamperti
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico C. Besta, 20126 Milan, Italy; (C.L.); (V.T.)
| | - Alessandro Prigione
- Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Clinic Düsseldorf (UKD), Heinrich Heine University (HHU), 40225 Dusseldorf, Germany;
| | - Valeria Tiranti
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico C. Besta, 20126 Milan, Italy; (C.L.); (V.T.)
| | - Nicola Persico
- Department of Clinical Science and Community Health, University of Milan, 20122 Milan, Italy;
- Fetal Medicine and Surgery Service, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Dario Brunetti
- Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico C. Besta, 20126 Milan, Italy; (C.L.); (V.T.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
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XRD and ATR-FTIR techniques for integrity assessment of gamma radiation sterilized cortical bone pretreated by antioxidants. Cell Tissue Bank 2020; 22:305-321. [PMID: 33165827 DOI: 10.1007/s10561-020-09879-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 10/30/2020] [Indexed: 01/22/2023]
Abstract
Terminal sterilization of bone allograft by gamma radiation is required to reduce the risk of infection. Free radical scavengers could be utilized to minimize the deteriorating effects of gamma radiation on bone allograft mechanical properties. The objective of this research is to assess the changes in structural and chemical composition induced by hydroxytyrosol (HT) and alpha lipoic acid (ALA) free radical scavengers in gamma sterilized cortical bone. Bovine femurs specimens were soaked in different concentrations of HT and ALA for 7 and 3 days respectively before irradiation with 35 KGy gamma radiation. The attenuated total reflection-Fourier transform infrared spectroscopy and the X-ray diffraction techniques were utilized to analyze the changes in chemical composition induced by irradiation in the presence of free radical scavengers. A significant increase in the proportion of amide I and amide II to phosphate was noticed in the irradiated group, while in the pretreated groups with ALA and HT this effect was minimized. In addition, gamma radiation reduced the mature to immature cross links while ALA and HT alleviated this reduction. No significant changes were noticed in the mineral crystallinity or crystal size. Bone chemical structure has been changed due to gamma irradiation and these changes are mainly relevant to amide I, amide II proportions and collagen crosslinks. The deteriorating effects of gamma sterilization dose (35 kGy) on chemical structure of bone allograft can be alleviated by using (HT) and (ALA) free radical scavengers before irradiation.
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El-Hansi NS, Sallam AM, Talaat MS, Said HH, Khalaf MA, Desouky OS. Biomechanical properties enhancement of gamma radiation-sterilized cortical bone using antioxidants. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2020; 59:571-581. [PMID: 32444954 DOI: 10.1007/s00411-020-00848-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 05/11/2020] [Indexed: 06/11/2023]
Abstract
Gamma radiation sterilization is the method used by the majority of tissue banks to reduce disease transmission from infected donors to recipients through bone allografts. However, many studies have reported that gamma radiation impairs the structural and mechanical properties of bone via formation of free radicals, the effect of which could be reduced using free radical scavengers. The aim of this study is to examine the radioprotective role of hydroxytyrosol (HT) and alpha lipoic acid (ALA) on the mechanical properties of gamma-sterilized cortical bone of bovine femur, using three-point bending and microhardness tests. Specimens of bovine femurs were soaked in ALA and HT for 3 and 7 days, respectively, before being exposed to 35-kGy gamma radiation. In unirradiated samples, both HT and ALA pre-treatment improved the cortical bone bending plastic properties (maximum bending stress, maximum bending strain, and toughness) without affecting microhardness. Irradiation resulted in a drastic reduction of the plastic properties and an increased microhardness. ALA treatment before irradiation alleviated the aforementioned reductions in maximum bending stress, maximum bending strain, and toughness. In addition, under ALA treatment, the microhardness was not increased after irradiation. For HT treatment, similar effects were found. In conclusion, the results indicate that HT and ALA can be used before irradiation to enhance the mechanical properties of gamma-sterilized bone allografts.
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Affiliation(s)
- Naglaa S El-Hansi
- Biophysics Lab, Radiation Physics Department, (NCRRT), Atomic Energy Authority (AEA), Nasr City, Cairo, Egypt
| | - Abdelsattar M Sallam
- Biophysics Branch, Physics Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Mona S Talaat
- Biophysics Branch, Physics Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hoda H Said
- Biophysics Lab, Radiation Physics Department, (NCRRT), Atomic Energy Authority (AEA), Nasr City, Cairo, Egypt.
| | - Mahmoud A Khalaf
- Microbiology Department (NCRRT), Atomic Energy Authority (AEA), Nasr City, Cairo, Egypt
| | - Omar S Desouky
- Biophysics Lab, Radiation Physics Department, (NCRRT), Atomic Energy Authority (AEA), Nasr City, Cairo, Egypt
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Makhova AA, Shikh EV, Bulko TV, Gilep AA, Usanov SA, Shumyantseva VV. No effect of lipoic acid on catalytic activity of cytochrome P450 3A4. Drug Metab Pers Ther 2020; 35:dmpt-2020-0105. [PMID: 32712589 DOI: 10.1515/dmpt-2020-0105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/13/2020] [Indexed: 01/10/2023]
Abstract
Objectives α-Lipoic acid is used as an antioxidant in multivitamin formulations to restore the normal level of intracellular glutathione after depletion caused by environmental pollutants or during physiological aging of the body, as a chelating agent, as a dietary supplement, in anti-aging compositions. Lipoic acid (LA) acts as a buffer in cancer therapy and in therapy of diseases associated with oxidative stress. The effect of LA on the catalytic functions of cytochrome P450 3A4 as the main enzyme of the biotransformation of drugs was studied. It was shown that LA in the concentration range of 50-200 μM affects the stage of electron transfer (stage of cytochrome P450 3A4 heme reduction), decreasing the cathodic reduction current by an average of 20 ± 5%. The kinetic parameters (k cat) of the N-demethylation reaction of erythromycin, the antibiotic of the macrolide group, used as a marker substrate for the comparative analysis of the catalytic activity of cytochrome P450 3A4, both in the presence of α-lipoic acid and in the cytochrome P450 3A4-erythromycin complex, amounted to comparable values of 3.5 ± 0.9 and 3.4 ± 0.9 min-1, respectively. Based on these experimental data, we can conclude that there is no significant effect of α-lipoic acid on the catalysis of cytochrome P450 3A4. These results can be projected on the possibility of using α-lipoic acid in complex therapy without negative impact on the enzymatic cytochrome P450 system. Methods The analysis was performed in electrochemical non-invasive model systems for recording the catalytic activity of cytochrome P450 3A4, using screen-printed electrodes, modified with membranous didodecyldimethylammonium bromide. Results It was shown that LA did not affect the N-demethylation of macrolide antibiotic erythromycin. Catalytic constant (k cat) of N-demethylation of erythromycin corresponds to 3.4 ± 0.9 min-1 and in the presence of LA corresponds to 3.5 ± 0.9 min-1. Conclusions Based on the obtained experimental data, we can conclude that there is no significant effect of α-lipoic acid on individual stages and processes of catalysis of cytochrome P450 3A4. LA can be recommended for inclusion in complex therapy as an antioxidant, antitoxic and chelating compound without negative impact on the enzymatic cytochrome P450 3A4 activity of the human body.
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Affiliation(s)
- Anna A Makhova
- Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Evgeniya V Shikh
- Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Tatiana V Bulko
- Institute of Biomedical Chemistry, Moscow, Russian Federation
| | | | | | - Victoria V Shumyantseva
- Institute of Biomedical Chemistry, Moscow, Russian Federation.,Pirogov Russian National Research Medical University, Moscow, Russian Federation
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Xiao L, Wei F, Zhou Y, Anderson GJ, Frazer DM, Lim YC, Liu T, Xiao Y. Dihydrolipoic Acid-Gold Nanoclusters Regulate Microglial Polarization and Have the Potential To Alter Neurogenesis. NANO LETTERS 2020; 20:478-495. [PMID: 31789044 DOI: 10.1021/acs.nanolett.9b04216] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Microglia-mediated neuroinflammation is one of the most significant features in a variety of central nervous system (CNS) disorders such as traumatic brain injury, stroke, and many neurodegenerative diseases. Microglia become polarized upon stimulation. The two extremes of the polarization are the neuron-destructive proinflammatory M1-like and the neuron-regenerative M2-like phenotypes. Thus, manipulating microglial polarization toward the M2 phenotype is a promising therapeutic approach for CNS repair and regeneration. It has been reported that nanoparticles are potential tools for regulating microglial polarization. Gold nanoclusters (AuNCs) could penetrate the blood-brain barrier and have neuroprotective effects, suggesting the possibility of utilizing AuNCs to regulate microglial polarization and improve neuronal regeneration in CNS. In the current study, AuNCs functionalized with dihydrolipoic acid (DHLA-AuNCs), an antioxidant with demonstrated neuroprotective roles, were prepared, and their effects on polarization of a microglial cell line (BV2) were examined. DHLA-AuNCs effectively suppressed proinflammatory processes in BV2 cells by inducing polarization toward the M2-like phenotype. This was associated with a decrease in reactive oxygen species and reduced NF-kB signaling and an improvement in cell survival coupled with enhanced autophagy and inhibited apoptosis. Conditioned medium from DHLA-AuNC-treated BV2 cells was able to enhance neurogenesis in both the neuronal cell line N2a and in an ex vivo brain slice stroke model. The direct treatment of brain slices with DHLA-AuNCs also ameliorated stroke-related tissue injury and reduced astrocyte activation (astrogliosis). This study suggests that by regulating neuroinflammation to improve neuronal regeneration, DHLA-AuNCs could be a potential therapeutic agent in CNS disorders.
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Affiliation(s)
- Lan Xiao
- Institute of Health and Biomedical Innovation , Queensland University of Technology , 60 Musk Avenue , Kelvin Grove, Brisbane , QLD 4059 , Australia
| | - Fei Wei
- Institute of Health and Biomedical Innovation , Queensland University of Technology , 60 Musk Avenue , Kelvin Grove, Brisbane , QLD 4059 , Australia
| | - Yinghong Zhou
- Institute of Health and Biomedical Innovation , Queensland University of Technology , 60 Musk Avenue , Kelvin Grove, Brisbane , QLD 4059 , Australia
- The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM) , https://research.qut.edu.au/accterm/
| | - Gregory J Anderson
- QIMR Berghofer Medical Research Institute , 300 Herston Road , Brisbane , QLD 4006 , Australia
| | - David M Frazer
- QIMR Berghofer Medical Research Institute , 300 Herston Road , Brisbane , QLD 4006 , Australia
| | - Yi Chieh Lim
- QIMR Berghofer Medical Research Institute , 300 Herston Road , Brisbane , QLD 4006 , Australia
| | - Tianqing Liu
- QIMR Berghofer Medical Research Institute , 300 Herston Road , Brisbane , QLD 4006 , Australia
| | - Yin Xiao
- Institute of Health and Biomedical Innovation , Queensland University of Technology , 60 Musk Avenue , Kelvin Grove, Brisbane , QLD 4059 , Australia
- The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM) , https://research.qut.edu.au/accterm/
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Anaraki MT, Lysak DH, Soong R, Simpson MJ, Spraul M, Bermel W, Heumann H, Gundy M, Boenisch H, Simpson AJ. NMR assignment of the in vivo daphnia magna metabolome. Analyst 2020; 145:5787-5800. [DOI: 10.1039/d0an01280g] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Daphnia (freshwater fleas) are among the most widely used organisms in regulatory aquatic toxicology/ecology, while their recent listing as an NIH model organism is stimulating research for understanding human diseases and processes.
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Affiliation(s)
| | | | - Ronald Soong
- Department of Physical and Environmental Sciences
- University of Toronto Scarborough
- Toronto
- Canada
| | - Myrna J. Simpson
- Department of Physical and Environmental Sciences
- University of Toronto Scarborough
- Toronto
- Canada
- Department of Chemistry
| | | | | | | | | | | | - André J. Simpson
- Department of Physical and Environmental Sciences
- University of Toronto Scarborough
- Toronto
- Canada
- Department of Chemistry
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43
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Determination of lipoic acid in human plasma by high-performance liquid chromatography with ultraviolet detection. ARAB J CHEM 2019. [DOI: 10.1016/j.arabjc.2016.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Jedidi S, Rtibi K, Selmi S, Aloui F, Selmi H, Wannes D, Sammari H, Dhawefi N, Chaâbane A, Sebai H. Phytochemical/Antioxidant Properties and Individual/Synergistic Actions of Salvia officinalis L. Aqueous Extract and Loperamide on Gastrointestinal Altering Motor Function. J Med Food 2019; 22:1235-1245. [DOI: 10.1089/jmf.2019.0051] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Affiliation(s)
- Saber Jedidi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
- Faculty of Sciences of Bizerte, University of Carthage, Zarzouna, Tunisia
| | - Kais Rtibi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Slimen Selmi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Foued Aloui
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
| | - Houcine Selmi
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
| | - Dalanda Wannes
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Houcem Sammari
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Nourhène Dhawefi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Abbes Chaâbane
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
| | - Hichem Sebai
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
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45
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Inactivation of Aldehyde Dehydrogenase by Disulfiram in the Presence and Absence of Lipoic Acid or Dihydrolipoic Acid: An in Vitro Study. Biomolecules 2019; 9:biom9080375. [PMID: 31426424 PMCID: PMC6723463 DOI: 10.3390/biom9080375] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/02/2019] [Accepted: 08/13/2019] [Indexed: 01/22/2023] Open
Abstract
The inhibition of aldehyde dehydrogenase (ALDH) by disulfiram (DSF) in vitro can be prevented and/or reversed by dithiothreitol (DTT), which is a well-known low molecular weight non-physiological redox reagent commonly used in laboratory experiments. These observations inspired us to ask the question whether the inhibition of ALDH by DSF can be preserved or abolished also by dihydrolipoic acid (DHLA), which is the only currently known low molecular weight physiological dithiol in the body of humans and other animals. It can even be metaphorized that DHLA is an "endogenous DTT". Lipoic acid (LA) is the oxidized form of DHLA. We investigated the inactivation of ALDH derived from yeast and rat liver by DSF in the presence or absence of LA or DHLA. The results clearly show that DHLA is able both to restore and protect ALDH activity blocked by DSF. The proposed mechanism is discussed.
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Schwantje M, de Sain‐van der Velden M, Jans J, van Gassen K, Dorrepaal C, Koop K, Visser G. Genetic defect of the sodium-dependent multivitamin transporter: A treatable disease, mimicking biotinidase deficiency. JIMD Rep 2019; 48:11-14. [PMID: 31392107 PMCID: PMC6606985 DOI: 10.1002/jmd2.12040] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 02/25/2019] [Accepted: 02/27/2019] [Indexed: 12/28/2022] Open
Abstract
The sodium-dependent multivitamin transporter that facilitates the uptake of the water-soluble vitamins biotin, pantothenic acid, and the vitamin-like substance lipoate is coded by the SLC5A6 gene. Variants in this gene cause a relatively novel treatable metabolic disorder. Here we describe the second case. A 17-month-old girl presented with hypoglycemia (2.0 mmol/L) and severe metabolic acidosis (pH 6.87), leading to resuscitation. Her history revealed feeding problems from birth and poor weight gain. Metabolic investigation showed elevated plasma C3-carnitine and C5-OH-carnitine. Urine analysis showed persistently elevated excretion of 3-OH-isovaleric acid. Biochemically, the combination of elevated C5-OH-carnitine and increased excretion of 3-OH-isovaleric acid seemed compatible with biotinidase deficiency. Supplementation with biotin was started. Biotinidase activity in plasma showed only marginally decreased activity, which was considered insufficient explanation for her clinical symptoms. Subsequent trio-based whole exome sequencing revealed compound heterozygosity for variants in the SLC5A6 gene. Upon increasing the dosage of biotin supplementation and introduction of pantothenic acid supplementation, a striking clinical improvement was seen.
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Affiliation(s)
- Marit Schwantje
- Department of GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
- Department of Metabolic DiseasesWilhelmina Children's Hospital, University Medical Center UtrechtUtrechtthe Netherlands
| | | | - Judith Jans
- Department of GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Koen van Gassen
- Department of GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
| | | | - Klaas Koop
- Department of Metabolic DiseasesWilhelmina Children's Hospital, University Medical Center UtrechtUtrechtthe Netherlands
| | - Gepke Visser
- Department of Metabolic DiseasesWilhelmina Children's Hospital, University Medical Center UtrechtUtrechtthe Netherlands
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Borowczyk K, Olejarz P, Chwatko G. Application of simultaneous separation and derivatization for the determination of α-lipoic acid in urine samples by high-performance liquid chromatography with spectrofluorimetric detection. Biomed Chromatogr 2019; 33:e4576. [PMID: 31069825 DOI: 10.1002/bmc.4576] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 04/26/2019] [Accepted: 05/02/2019] [Indexed: 01/17/2023]
Abstract
To help to clarify therapeutic functions of lipoic acid (LA) in biochemical and clinical practice we have elaborated a fast, simple and accurate HPLC method enabling determination of LA in human urine. The proposed analytical approach includes reduction of LA with tris(2-carboxyethyl)phosphine and simultaneous separation and derivatization of the analyte with butylamine and o-phthaldialdehyde followed by spectrofluorimetric detection at λex = 340 nm and λem = 440 nm. The assay was performed using gradient elution and the mobile phase containing 0.0025 mol L-1 o-phthaldialdehyde in 0.0025 mol L-1 NaOH and acetonitrile. Linearity of the detector response for LA was observed in the range of 0.3-8 μmol L-1 . Limits of detection and quantification for LA in urine samples were 0.02 and 0.03 μmol L-1 , respectively. The total analysis time, including sample work-up, was <20 min. The analytical procedure was successfully applied to analysis of real urine samples delivered from six healthy volunteers who received a single 100 mg dose of LA.
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Affiliation(s)
- Kamila Borowczyk
- Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland
| | - Patrycja Olejarz
- Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland
| | - Grażyna Chwatko
- Department of Environmental Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland
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48
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Valdecantos MP, Pérez-Matute P, Prieto-Hontoria P, Moreno-Aliaga MJ, Martínez JA. Impact of dietary lipoic acid supplementation on liver mitochondrial bioenergetics and oxidative status on normally fed Wistar rats. Int J Food Sci Nutr 2019; 70:834-844. [PMID: 30764676 DOI: 10.1080/09637486.2019.1572716] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The aim of this study was to examine the effects of α-lipoic acid (α-LA) on liver mitochondrial bioenergetics and oxidative status for 8 weeks in normal-healthy animals. A pair-fed group was included to differentiate between α-LA direct effects and those changes due to reduced food intake. α-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. α-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. α-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all β-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in α-LA-treated animals. Thus, α-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when α-LA is administered or recommended to a healthy population.
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Affiliation(s)
- M P Valdecantos
- Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM) , Madrid , Spain.,Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), Instituto de Salud Carlos III , Madrid , Spain.,Department of Nutrition, Food Science and Physiology, University of Navarra , Pamplona , Spain
| | - P Pérez-Matute
- Department of Nutrition, Food Science and Physiology, University of Navarra , Pamplona , Spain.,Department of Infectious Diseases, Infectious Diseases, Microbiota and Metabolism Unit, Center for Biomedical Research of La Rioja (CIBIR) , Logroño, Spain
| | - P Prieto-Hontoria
- Department of Nutrition, Food Science and Physiology, University of Navarra , Pamplona , Spain
| | - M J Moreno-Aliaga
- Department of Nutrition, Food Science and Physiology, University of Navarra , Pamplona , Spain.,Centre for Nutrition Research, University of Navarra , Pamplona , Spain.,CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn) , Madrid , Spain.,IdiSNA, Navarra's Health Research Institute , Pamplona , Spain
| | - J A Martínez
- Department of Nutrition, Food Science and Physiology, University of Navarra , Pamplona , Spain.,Centre for Nutrition Research, University of Navarra , Pamplona , Spain.,CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn) , Madrid , Spain.,IdiSNA, Navarra's Health Research Institute , Pamplona , Spain.,IMDEA Food Institute, CEI UAM + CSIC , Madrid , Spain
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Rehman MU, Wali AF, Ahmad A, Shakeel S, Rasool S, Ali R, Rashid SM, Madkhali H, Ganaie MA, Khan R. Neuroprotective Strategies for Neurological Disorders by Natural Products: An update. Curr Neuropharmacol 2019; 17:247-267. [PMID: 30207234 PMCID: PMC6425075 DOI: 10.2174/1570159x16666180911124605] [Citation(s) in RCA: 133] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Revised: 08/02/2018] [Accepted: 09/05/2018] [Indexed: 01/30/2023] Open
Abstract
Nature has bestowed mankind with surplus resources (natural products) on land and water. Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. These natural products have been experimentally documented to possess various biological properties such as antioxidant, anti-inflammatory and anti-apoptotic activities. In vitro and in vivo studies have further established the usefulness of natural products in various preclinical models of neurodegenerative disorders. Natural products include phytoconstituents, like polyphenolic antioxidants, found in herbs, fruits, nuts, vegetables and also in marine and freshwater flora. These phytoconstituents may potentially suppress neurodegeneration and improve memory as well as cognitive functions of the brain. Also, they are known to play a pivotal role in the prevention and cure of different neurodegenerative diseases, such as Alzheimer's disease, epilepsy, Parkinson's disease and other neuronal disorders. The large-scale neuro-pharmacological activities of natural products have been documented due to the result of either the inhibition of inflammatory processes, or the up-regulation of various cell survival proteins or a combination of both. Due to the scarcity of human studies on neuroprotective effects of natural products, this review focuses on the various established activities of natural products in in vitro and in vivo preclinical models, and their potential neuro-therapeutic applications using the available knowledge in the literature.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Rehan Khan
- Address correspondence to this author at the Department of Nano-Therapeutics, Institute of Nano Science & Technology, Habitat Centre, Phase X, Mohali-160062, Punjab, India; E-mail:
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El-Gebaly RH, Rageh MM, Maamoun IK. Radio-protective potential of lipoic acid free and nano-capsule against 99mTc-MIBI induced injury in cardio vascular tissue. JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY 2019; 27:83-96. [PMID: 30507603 DOI: 10.3233/xst-180438] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
BACKGROUND SPECT MPI (Single photon emission computed tomography myocardial perfusion imaging) is an essential tool for diagnosis of cardiovascular disease, but it also involves considerable exposure to ionizing radiation. OBJECTIVE To determine the radioprotective potential of lipoic acid free and nano-capsule against 99mTc-MIBI-induced injury in cardiovascular tissue. METHODS The radioprotective ability was assessed by blood count, histopathology and heart enzymes in different groups of mice. Hearts of mice from all groups were dissected and prepared for oxidative stress analysis of superoxide dismutase (SOD) and malondialdehyde (MDA). Furthermore, levels of DNA damage in heart and bone marrow cells were evaluated by alkaline comet assay technique. The same measurements were estimated after treating the mice with lipoic acid. RESULTS Comparing mice injected by radiopharmaceutics with control group showed a significant depression in the count of white blood cells (WBC) by about 40 % at 24 &72 hrs post-radiopharmaceutical administration. Moreover, platelets count was decreased by 27% at 72 hrs post-radiopharmaceutical administration. Radiation also dropped in super oxide dismutase (SOD) and increased in activity of heart enzymes and level of MDA (Malondialdehyde). Additionally, histopathological observation was characterized by focal necrosis of cardiac myocytes. 99mTc-MIBI induced DNA damage had significant increase. Nevertheless, pretreatment with free and lipoic acid nano-capsules (LANC's) prevented the reduction induced in WBCs and platelets, and improved their counts significantly. Conversely pre-treatment with lipoic acid free and nano-capsule significantly increased the activity of SOD and decreased the level of MDA and therefore protected the cardiovascular tissues and reduced DNA strand-break, consequently and enhanced the body weight of the mice. CONCLUSIONS These findings highlight the efficacy of lipoic acid free and nano-capsule as a radio protector.
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Affiliation(s)
- Reem H El-Gebaly
- Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt
| | - Monira M Rageh
- Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt
| | - Islam K Maamoun
- Intensive Care Unit, Faculty of Medicine, Cairo University, Giza, Egypt
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