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Tumentemur G, Titiz M, Ors AB. Metabolic intervention restores fertility and sperm health in non-obese diabetic rats. Front Endocrinol (Lausanne) 2025; 16:1558769. [PMID: 40331141 PMCID: PMC12051186 DOI: 10.3389/fendo.2025.1558769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 03/03/2025] [Indexed: 05/08/2025] Open
Abstract
Background In people with diabetes, the effect of sleeve gastrectomy on impaired sperm parameters, hormonal profile, and testis tissue remains controversial to some extent. The context and purpose of the study This study aimed to investigate the effects of sleeve gastrectomy on the hormonal profile, sperm parameters, and testis tissue in infertile rats with type II diabetes mellitus (TIIDM). This study included 32 rats with TIIDM with or without sleeve gastrectomy. All the rats underwent sperm, testis tissue, and serum hormone profile analyses before and 8 weeks after surgery. Results There was a significant correlation between weight loss after sleeve gastrectomy and a decrease in glucose profile (p < 0.05). In the hormonal profile, testosterone improved significantly after 8 weeks following sleeve gastrectomy. There was a significant increase in sperm count (p < 0.05) and improved sperm morphology during the follow-up after sleeve gastrectomy. The analysis also showed significant changes in testis tissue after surgery. Conclusion Sleeve gastrectomy significantly improved testosterone deficiency, testis tissue, and sperm count in rats with TIIDM. Further prospective clinical studies are needed to show how bariatric surgery affects infertility in patients with TIIDM.
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Affiliation(s)
- Gamze Tumentemur
- Acibadem University Vocational School of Health Services, Istanbul, Türkiye
| | - Mustafa Titiz
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Tuscany, Italy
| | - Alev Bobus Ors
- Faculty of Medicine, Mersin University, Yenişehir, Mersin, Türkiye
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Stojchevski R, Velichkovikj S, Bogdanov J, Hadzi-Petrushev N, Mladenov M, Poretsky L, Avtanski D. Monocarbonyl analogs of curcumin C66 and B2BrBC modulate oxidative stress, JNK activity, and pancreatic gene expression in rats with streptozotocin-induced diabetes. Biochem Pharmacol 2024; 229:116491. [PMID: 39147331 DOI: 10.1016/j.bcp.2024.116491] [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: 03/29/2024] [Revised: 07/26/2024] [Accepted: 08/13/2024] [Indexed: 08/17/2024]
Abstract
The pathogenesis of type 1 diabetes mellitus (T1DM) involves oxidative stress and inflammation. Curcumin, a natural polyphenolic compound found in turmeric, known to exhibit antioxidative and anti-inflammatory properties, is characterized by poor chemical stability, low bioavailability, and rapid metabolism. Monocarbonyl analogs of curcumin (MACs) with a structural absence of β-diketone and enhanced stability and bioavailability present a potential solution to the challenges associated with the use of curcumin. This study aimed to evaluate the effect of two MACs, C66 and B2BrBC, on oxidative stress markers, antioxidant enzyme activity, expression of diabetes-associated genes, and signaling pathway proteins in the context of T1DM. Streptozotocin (STZ)-induced male Wistar rats or rat pancreatic RIN-m cells were used for in vivo and in vitro experiments, respectively. C66 or B2BrBC were given either before or after STZ treatment. Oxidative stress markers and antioxidant enzyme activities were determined in various tissues. Expression of diabetes-associated genes was assessed using RT-qPCR, and the activity of signaling pathway proteins in the pancreas was determined through Western blot analysis. Treatment with C66 and B2BrBC significantly reduced oxidative stress markers and positively influenced antioxidant enzyme activities. Moreover, both compounds inhibited JNK activity in the pancreas while enhancing the expression of genes crucial for β-cell survival and glucose and redox homeostasis. The findings highlight the multifaceted potential of C66 and B2BrBC in ameliorating oxidative stress, influencing gene expression patterns linked to diabetes, and modulating key signaling pathways in the pancreas. The findings suggest that these compounds can potentially address diabetes-related pathological processes.
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Affiliation(s)
- Radoslav Stojchevski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Feinstein Institutes for Medical Research, Manhasset, NY, USA
| | - Sara Velichkovikj
- Department of Medicine, Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Jane Bogdanov
- Faculty of Natural Sciences and Mathematics, Institute of Chemistry, Ss. Cyril and Methodius University, Skopje, Macedonia
| | - Nikola Hadzi-Petrushev
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, Skopje, Macedonia
| | - Mitko Mladenov
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, Skopje, Macedonia
| | - Leonid Poretsky
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Feinstein Institutes for Medical Research, Manhasset, NY, USA
| | - Dimiter Avtanski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Feinstein Institutes for Medical Research, Manhasset, NY, USA.
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Nath A, Ghosh S, Bandyopadhyay D. Role of melatonin in mitigation of insulin resistance and ensuing diabetic cardiomyopathy. Life Sci 2024; 355:122993. [PMID: 39154810 DOI: 10.1016/j.lfs.2024.122993] [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: 06/11/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 08/20/2024]
Abstract
Addressing insulin resistance or hyperinsulinemia might offer a viable treatment approach to stop the onset of diabetic cardiomyopathy, as these conditions independently predispose to the development of the disease, which is initially characterized by diastolic abnormalities. The development of diabetic cardiomyopathy appears to be driven mainly by insulin resistance or impaired insulin signalling and/or hyperinsulinemia. Oxidative stress, hypertrophy, fibrosis, cardiac diastolic dysfunction, and, ultimately, systolic heart failure are the outcomes of these pathophysiological alterations. Melatonin is a ubiquitous indoleamine, a widely distributed compound secreted mainly by the pineal gland, and serves a variety of purposes in almost every living creature. Melatonin is found to play a leading role by improving myocardial cell metabolism, decreasing vascular endothelial cell death, reversing micro-circulation disorders, reducing myocardial fibrosis, decreasing oxidative and endoplasmic reticulum stress, regulating cell autophagy and apoptosis, and enhancing mitochondrial function. This review highlights a relationship between insulin resistance and associated cardiomyopathy. It explores the potential therapeutic strategies offered by the neurohormone melatonin, an important antioxidant that plays a leading role in maintaining glucose homeostasis by influencing the glucose transporters independently and through its receptors. The vast distribution of melatonin receptors in the body, including beta cells of pancreatic islets, asserts the role of this indole molecule in maintaining glucose homeostasis. Melatonin controls the production of GLUT4 and/or the phosphorylation process of the receptor for insulin and its intracellular substrates, activating the insulin-signalling pathway through its G-protein-coupled membrane receptors.
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Affiliation(s)
- Anupama Nath
- Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, University College of Science, Technology and Agriculture, 92 APC Road, Kolkata 700 009, India
| | - Songita Ghosh
- Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, University College of Science, Technology and Agriculture, 92 APC Road, Kolkata 700 009, India
| | - Debasish Bandyopadhyay
- Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University of Calcutta, University College of Science, Technology and Agriculture, 92 APC Road, Kolkata 700 009, India.
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El-Sayed NS, Khalil NA, Saleh SR, Aly RG, Basta M. The Possible Neuroprotective Effect of Caffeic Acid on Cognitive Changes and Anxiety-Like Behavior Occurring in Young Rats Fed on High-Fat Diet and Exposed to Chronic Stress: Role of β-Catenin/GSK-3B Pathway. J Mol Neurosci 2024; 74:61. [PMID: 38954245 DOI: 10.1007/s12031-024-02232-4] [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: 01/09/2024] [Accepted: 05/28/2024] [Indexed: 07/04/2024]
Abstract
Lifestyle influences physical and cognitive development during the period of adolescence greatly. The most important of these lifestyle factors are diet and stress. Therefore, the aim of this study was to investigate the impact of high fat diet (HFD) and chronic mild stress on cognitive function and anxiety-like behaviors in young rats and to study the role of caffeic acid as a potential treatment for anxiety and cognitive dysfunction. Forty rats were assigned into 4 groups: control, HFD, HFD + stress, and caffeic acid-treated group. Rats were sacrificed after neurobehavioral testing. We detected memory impairment and anxiety-like behavior in rats which were more exaggerated in stressed rats. Alongside the behavioral changes, there were biochemical and histological changes. HFD and/or stress decreased hippocampal brain-derived neurotrophic factor (BDNF) levels and induced oxidative and inflammatory changes in the hippocampus. In addition, they suppressed Wnt/β-catenin pathway which was associated with activation of glycogen synthase kinase 3β (GSK3β). HFD and stress increased arginase 1 and inducible nitric oxide synthase (iNOS) levels as well. These disturbances were found to be aggravated in stressed rats than HFD group. However, caffeic acid was able to reverse these deteriorations leading to memory improvement and ameliorating anxiety-like behavior. So, the current study highlights an important neuroprotective role for caffeic acid that may guard against induction of cognitive dysfunction and anxiety disorders in adolescents who are exposed to HFD and/or stress.
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Affiliation(s)
- Norhan S El-Sayed
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
- Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
| | - Nehal Adel Khalil
- Department of Medical Biochemistry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Samar R Saleh
- Department of Biochemistry, Faculty of Science, Alexandria University, Baghdad St., Moharam Bek, Alexandria, 21511, Egypt
- Bioscreening and Preclinical Trial Lab, Department of Biochemistry, Faculty of Science, Alexandria University, Baghdad St., Moharam Bek, Alexandria, 21511, Egypt
| | - Rania G Aly
- Department of pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Marianne Basta
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
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Abudigin WI, Bajaber A, Subash-Babu P. Impact of various dietary lipids on amelioration of biomarkers linked to metabolic syndrome in both healthy and diabetic Wistar rats. BMC Nutr 2024; 10:75. [PMID: 38755663 PMCID: PMC11097575 DOI: 10.1186/s40795-024-00881-7] [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: 02/01/2024] [Accepted: 05/07/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND The present study was designed to investigate the influence of different dietary lipids (sheep's fat, olive oil, coconut oil, and corn oil) on specific biomarkers associated with metabolic syndrome in both healthy and diabetic rats. METHODS The study designed for 45 days, utilized a male diabetic wistar rat (body weight, 180-220 g) model induced by streptozotocin (45 mg/kg bw). The rats were divided into two sections: five non-diabetic and five diabetic groups, each containing six rats. The first group in each section serving as the control, received a standard diet. Both non-diabetic or diabetic groups, were provided with a standard diet enriched with 15% sheep fat, 15% coconut oil, 15% olive oil, and 15% corn oil, respectively for a duration of 45 days. RESULTS Post-supplementation, both healthy and diabetic control rats exhibited a higher food intake compared to rats supplemented with lipid diet; notably food intake was higher in diabetic control than healthy control. However, rats fed with coconut oil, olive oil and sheep fat showed weight gain at the end of the experiment, in both healthy and diabetic groups. Coconut oil supplementation significantly (p ≤ 0.05) increased HDL-C and total cholesterol level in diabetic groups compared to healthy group, it was confirmed by an increased PPAR-α and ABCA-1 protein level. Olive oil significantly decreased triglyceride, total cholesterol, and LDL-C levels in diabetic rats when compared to sheep fat or coconut oil. Corn oil significantly decreased fasting glucose, total cholesterol and LDL-C levels compared to all other groups. Corn and olive oil supplemented normal groups, found with significant increase in hepatic glucose-lipid oxidative metabolism associated protein, like FGF-21, MSH, ABCA-1, PPAR-γ and decreased lipogenesis proteins like, SREBP and PPAR-α levels. In contrast, sheep grease and coconut oil increased SREBP and PPAR-α expression in both normal and diabetic groups. Most notably, normal and diabetic groups pretreated with sheep grease resulted in increased inflammatory (MCP-1, IL-1β, TLR-4, TNF-α), and oxidative stress markers (LPO, GSH, GPx, SOD and CAT) linked with metabolic complications. CONCLUSION The combination or alternative use of olive oil and corn oil in daily diet may play a significant role in preventing proinflammatory condition associated with insulin resistance and cardiovascular diseases.
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Affiliation(s)
- Weaam I Abudigin
- Department of Food Science and Nutrition, College of Food & Agriculture Sciences, King Saud University, P.O. Box 22452, Riyadh, 11459, Saudi Arabia.
| | - Adnan Bajaber
- Department of Food Science and Nutrition, College of Food & Agriculture Sciences, King Saud University, P.O. Box 22452, Riyadh, 11459, Saudi Arabia
| | - Pandurangan Subash-Babu
- Department of Food Science and Nutrition, College of Food & Agriculture Sciences, King Saud University, P.O. Box 22452, Riyadh, 11459, Saudi Arabia
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Aluwong T, Sumanu VO, Abdulsalam RA, Emmanuel DS, Ezekiel NG, Aliyu MB, Ayo JO, Ukwenu JO, Yaro JD, Ogbuagu NE. Melatonin and probiotic administration ameliorated hyperglycaemia, oxidative stress, and enhanced cytoprotective effect on beta-cells of diabetic rats. J Diabetes Metab Disord 2023; 22:1537-1549. [PMID: 37975141 PMCID: PMC10638259 DOI: 10.1007/s40200-023-01284-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 08/16/2023] [Indexed: 11/19/2023]
Abstract
Objective The study aimed at investigating the effects of administering melatonin and a probiotic to streptozotocin-induced diabetic rats on hyperglycaemia, oxidative stress biomarkers and beta-cells. Design Type 1 diabetes was induced in 5 months-old male Wistar rats by single intraperitoneal (i.p.) administration of freshly-prepared STZ (60 mg/kg body weight). Six groups of 10 rats were used and treated once daily for six weeks; (1) Healthy control: normal saline only; (2) Pre-treated with Melatonin (MEL); (3) Diabetic control; (4) Diabetic + Treated with MEL; (5) Diabetic + Treated with Probiotic (Prob); (6) Diabetic + Treated with MEL + Prob. Blood glucose, body weight, activities of antioxidant enzymes and malondialdehyde concentration in serum and tissues, reduced glutathione and immunohistochemical assay. Data obtained were expressed as mean ± standard error of the mean (Mean ± SEM) and subjected to ANOVA followed by Tukey's post hoc test. Results Melatonin + Probiotic significantly decreased blood glucose concentrations in diabetic treated rats, compared to the diabetic control rats. MEL + Probiotic increased (p < 0.05) superoxide dismutase activity in serum and liver of diabetic rats. MEL + Probiotic reduced (p < 0.05) malondialdehyde concentration in the serum, liver and kidneys, respectively. MEL + Probiotic treated diabetic rats displayed islets with much greater content of insulin. Conclusion Melatonin + Probiotic combination was more effective in mitigating hyperglycaemia, oxidative stress, and exerted cytoprotective effect on the beta-cells.
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Affiliation(s)
- Tagang Aluwong
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
| | - Victory Osirimade Sumanu
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
| | | | - David Smith Emmanuel
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
| | - Nanyil Gunshin Ezekiel
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
| | - Muhammad Bello Aliyu
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
| | - Joseph Olusegun Ayo
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
| | | | - Jigo Dangude Yaro
- Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
| | - Ngozi Ejum Ogbuagu
- Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria
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Ertik O, Bayrak BB, Sener G, Yanardag R. Melatonin improves liver and pancreatic tissue injuries in diabetic rats: role on antioxidant enzymes. J Diabetes Metab Disord 2023; 22:591-602. [PMID: 37255817 PMCID: PMC10225460 DOI: 10.1007/s40200-022-01179-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 12/14/2022] [Accepted: 12/25/2022] [Indexed: 06/01/2023]
Abstract
Purpose Melatonin (Mel) is an indolamine mainly synthesized by the pineal gland and many other organs. It plays an important role in scavenging free radicals and stimulating antioxidant enzymes. The goal of this study was to investigate the effect of Mel and/or insulin treatment on oxidative liver and pancreas injuries in diabetic rats. Methods Male Wistar albino rats were assigned into 5 groups. Group I: control animals. Group II: diabetes was induced via a single dose of STZ (60 mg/kg) administered intraperitoneally. Group III: diabetic rats treated with Mel (10 mg/kg/day). Group IV: diabetic rats given insulin (6U/kg) subcutaneously. Group V: diabetic rats that received insulin and Mel at the same dose and time. After 12 weeks of the experiment, the animals were decapitated, liver and pancreas tissues were collected. Results The results indicated that reduced glutathione levels in liver and pancreatic tissue decreased, while protein carbonyl, advanced oxidized protein products and lipid peroxidation levels were elevated in diabetic group. Antioxidant enzyme activities decreased in liver tissues but increased in pancreatic tissues of the diabetic group. Administration of Mel, insulin or Mel + insulin reversed these biochemical changes in the diabetic animals. Conclusion This work shows that in long-term oxidative stress conditions caused by STZ-induced diabetes, either Mel or Mel + insulin administration may improve the deteriorated oxidant/antioxidant system in both the liver and pancreas tissues. These results suggested that Mel alone or Mel + insulin treatments might have a significant role in protecting against liver and pancreatic damage in STZ diabetic rats via different antioxidant effects.
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Affiliation(s)
- Onur Ertik
- Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpaşa, 34320 Avcilar Istanbul, Turkey
| | - Bertan Boran Bayrak
- Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpaşa, 34320 Avcilar Istanbul, Turkey
| | - Goksel Sener
- Department of Pharmacology, Faculty of Pharmacy, Fenerbahce University, 34758 Ataşehir Istanbul, Turkey
| | - Refiye Yanardag
- Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpaşa, 34320 Avcilar Istanbul, Turkey
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Rahbarghazi A, Alamdari KA, Rahbarghazi R, Salehi-Pourmehr H. Co-administration of exercise training and melatonin on the function of diabetic heart tissue: a systematic review and meta-analysis of rodent models. Diabetol Metab Syndr 2023; 15:67. [PMID: 37005639 PMCID: PMC10067225 DOI: 10.1186/s13098-023-01045-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 03/27/2023] [Indexed: 04/04/2023] Open
Abstract
PURPOSE Diabetes mellitus (DM), a hyperglycemic condition, occurs due to the failure of insulin secretion and resistance. This study investigated the combined effects of exercise training and melatonin (Mel) on the function of heart tissue in diabetic rodent models. METHODS A systematic search was conducted in Embase, ProQuest, Cochrane library, Clinicaltrial.gov, WHO, Google Scholar, PubMed, Ovid, Scopus, Web of Science, Ongoing Trials Registers, and Conference Proceedings in July 2022 with no limit of date or language. All trials associated with the effect of Mel and exercise in diabetic rodent models were included. Of the 962 relevant publications, 58 studies met our inclusion criteria as follows; Mel and type 1 DM (16 studies), Mel and type 2 DM (6 studies), exercise and type 1 DM (24 studies), and exercise and type 2 DM (12 studies). Meta-analysis of the data was done using the Mantel Haenszel method. RESULTS In most of these studies, antioxidant status and oxidative stress, inflammatory response, apoptosis rate, lipid profiles, and glucose levels were monitored in diabetic heart tissue. According to our findings, both Mel and exercise can improve antioxidant capacity by activating antioxidant enzymes compared to the control diabetic groups (p < 0.05). The levels of pro-inflammatory cytokines, especially TNF-α were reduced in diabetic rodents after being treated with Mel and exercise. Apoptotic changes were diminished in diabetic rodents subjected to the Mel regime and exercise in which p53 levels and the activity of Caspases reached near normal levels (p < 0.05). Based on the data, both Mel and exercise can change the lipid profile in diabetic rodents, especially rats, and close it to near-to-control levels. CONCLUSION These data showed that exercise and Mel can reduce the harmful effects of diabetic conditions on the heart through the regulation of lipid profile, antioxidant capacity, apoptosis, and inflammation.
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Affiliation(s)
- Afshin Rahbarghazi
- Department of Physical Education and Sports Sciences, Faculty of Educational Science and Psychology, University of Mohaghegh Ardabil, Daneshgah Street, Ardabil, 56199-11367 Iran
- Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, Iran
| | | | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, Iran
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
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Dammak A, Pastrana C, Martin-Gil A, Carpena-Torres C, Peral Cerda A, Simovart M, Alarma P, Huete-Toral F, Carracedo G. Oxidative Stress in the Anterior Ocular Diseases: Diagnostic and Treatment. Biomedicines 2023; 11:biomedicines11020292. [PMID: 36830827 PMCID: PMC9952931 DOI: 10.3390/biomedicines11020292] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases.
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El-Sayed NS, Elatrebi S, Said R, Ibrahim HF, Omar EM. Potential mechanisms underlying the association between type II diabetes mellitus and cognitive dysfunction in rats: a link between miRNA-21 and Resveratrol's neuroprotective action. Metab Brain Dis 2022; 37:2375-2388. [PMID: 35781592 PMCID: PMC9581846 DOI: 10.1007/s11011-022-01035-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 06/13/2022] [Indexed: 11/10/2022]
Abstract
Cognitive impairment is considered as a typical feature of neurodegenerative diseases in diabetes mellitus (DM). However, the exact link between cognitive dysfunction and diabetes mellitus is still vague. This study aims to investigate some of the mechanisms underlying cognitive impairment that associates diabetes mellitus and insulin resistance. We investigated the role of resveratrol as well on cognitive function in experimentally induced type 2 diabetes highlighting on its influence on the expression of brain miRNA 21. Resveratrol is a naturally occurring, biologically active compound that has numerous significant impacts on the body. Type 2 diabetes mellitus was induced by high fat diet followed a single dose of streptozotocin. Diabetic rats were treated with resveratrol for four weeks. Rats were sacrificed after neurobehavioral testing. Hippocampal tissues were used to assess expression of miRNA 21, GSK and oxidative stress markers. Serum samples were obtained to determine glucose levels, lipid profile and insulin levels. Hippocampal and serum AGEs were measured as well and HOMA IR was calculated. We detected memory impairment and disturbed insulin signaling in diabetic rats. These derangements were reversed by resveratrol treatment partially due to increased expression of miRNA-21. Our study pins the role of miRNA-21 in modulating brain insulin signaling and hence alleviating cognitive dysfunction accompanying diabetes mellitus.
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Affiliation(s)
- Norhan S. El-Sayed
- Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Soha Elatrebi
- Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Rasha Said
- Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Heba F. Ibrahim
- Department of Histology and Cell Biology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Eman M. Omar
- Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Kuo CS, Chen CY, Huang HL, Tsai HY, Chou RH, Wei JH, Huang PH, Lin SJ. Melatonin Improves Ischemia-Induced Circulation Recovery Impairment in Mice with Streptozotocin-Induced Diabetes by Improving the Endothelial Progenitor Cells Functioning. Int J Mol Sci 2022; 23:ijms23179839. [PMID: 36077238 PMCID: PMC9456213 DOI: 10.3390/ijms23179839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/16/2022] Open
Abstract
Patients with diabetes mellitus tend to develop ischemia-related complications and have compromised endothelial progenitor cell (EPC) function. Melatonin protects against ischemic injury, possibly via EPC modulation. We investigated whether melatonin pretreatment could restore EPC function impairment and improve circulation recovery in a diabetic critical limb ischemia mouse model. Under 25 mM high-glucose medium in vitro, EPC proliferation, nitric oxide production, tube formation, and endothelial nitric oxide synthase (eNOS) phosphorylation were significantly suppressed. Hyperglycemia promoted EPC senescence and apoptosis as well as increased reactive oxygen species (ROS) production. Melatonin treatment reversed the harmful effects of hyperglycemia on EPC through adenosine monophosphate–activated protein kinase-related mechanisms to increase eNOS phosphorylation and heme oxygenase-1 expression. In an in-vivo study, after a 4-week surgical induction of hindlimb ischemia, mice with streptozotocin (STZ)-induced diabetes showed significant reductions in new vessel formation, tissue reperfusion, and EPC mobilization in ischemic hindlimbs compared to non-diabetic mice. Mice with STZ-induced diabetes that received melatonin treatment (10 mg/kg/day, intraperitoneal) had significantly improved blood perfusion ratios of ischemic to non-ischemic limb, EPC mobilization, and densities of capillaries. In addition, a murine bone marrow transplantation model to support these findings demonstrated that melatonin stimulated bone marrow-originated EPCs to differentiate into vascular endothelial cells in femoral ligation-induced ischemic muscles. In summary, this study suggests that melatonin treatment augments EPC function along with neovascularization in response to ischemia in diabetic mice. We illustrated the protective effects of melatonin on EPC H2O2 production, senescence, and migration through melatonin receptors and modulating eNOS, AMPK, and HO-1 activities at the cellular level. Thus, melatonin might be used to treat the impairment of EPC mobilization and circulation recuperation in response to ischemic injury caused by chronic hyperglycemia. Additional studies are needed to elucidate the applicability of the results in humans.
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Affiliation(s)
- Chin-Sung Kuo
- Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Chi-Yu Chen
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Hsin-Lei Huang
- Department of Nursing, College of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan
- Correspondence: (H.-L.H.); (P.-H.H.); Tel.: +886-2-2871-2121 (H.-L.H.); +886-2-2875-7434 (P.-H.H.); Fax: +886-2-2875-7435 (H.-L.H. & P.-H.H.)
| | - Hsiao-Ya Tsai
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Ruey-Hsing Chou
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- Cardiovascular Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Jih-Hua Wei
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Division of Cardiology, Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan 330056, Taiwan
- Department of Nutrition and Health Sciences, School of Healthcare Management, Kai-Nan University, Taoyuan 338103, Taiwan
| | - Po-Hsun Huang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- Cardiovascular Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- Correspondence: (H.-L.H.); (P.-H.H.); Tel.: +886-2-2871-2121 (H.-L.H.); +886-2-2875-7434 (P.-H.H.); Fax: +886-2-2875-7435 (H.-L.H. & P.-H.H.)
| | - Shing-Jong Lin
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- Cardiovascular Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- Taipei Heart Institute, Taipei Medical University, Taipei 110301, Taiwan
- Division of Cardiology, Heart Center, Cheng-Hsin General Hospital, Taipei 112401, Taiwan
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12
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Bostancıeri N, Elbe H, Eşrefoğlu M, Vardı N. Cardioprotective potential of melatonin, quercetin and resveratrol in an experimental model of diabetes. Biotech Histochem 2021; 97:152-157. [PMID: 33906539 DOI: 10.1080/10520295.2021.1918766] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Oxygen radicals participate in the pathogenesis of heart damage. Diabetes accelerates the formation of reactive oxygen species (ROS). We investigated the effects of the antioxidants, melatonin, quercetin and resveratrol, on cardiomyopathy and apoptosis in rats with streptozotocin (STZ) induced diabetes mellitus (DM). Rats were divided into five groups of seven: control, DM, DM + melatonin, DM + quercetin and DM + resveratrol. All treatments were begun with a single dose of STZ to induce diabetes and experimental treatments were continued daily for 30 days. Morphologic and apoptotic changes were analyzed by histological assessment. The heart tissue of the control group exhibited normal histology, whereas the heart tissue of the DM group exhibited vacuolization, necrosis, congestion, infiltration and myofibril loss. The DM group exhibited significantly increased apoptosis compared to the control group. Differences in anti-apoptotic effects were statistically significant for all three antioxidant treatment groups; the anti-apoptotic effects of quercetin and resveratrol were similar. Melatonin, resveratrol and quercetin exhibited protective effects against diabetic heart damage.
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Affiliation(s)
- N Bostancıeri
- Department of Histology and Embryology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - H Elbe
- Department of Histology and Embryology, Faculty of Medicine, Sıtkı Koçman University, Muğla, Turkey
| | - M Eşrefoğlu
- Department of Histology and Embryology, Faculty of Medicine, Bezmiâlem University, İstanbul, Turkey
| | - N Vardı
- Department of Histology and Embryology, Faculty of Medicine, Inönü University, Malatya, Turkey
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13
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ÇAKINA S, ÖZTÜRK Ş. Streptozotosin kaynaklı diyabetik sıçanların karaciğerindeki oksidatif stres belirteçleri: metformin ve sitagliptinin etkileri. CUKUROVA MEDICAL JOURNAL 2020. [DOI: 10.17826/cumj.791369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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14
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Saleh DO, Jaleel GAA, Al-Awdan SW, Hassan A, Asaad GF. Melatonin suppresses the brain injury after cerebral ischemia/reperfusion in hyperglycaemic rats. Res Pharm Sci 2020; 15:418-428. [PMID: 33628283 PMCID: PMC7879790 DOI: 10.4103/1735-5362.297844] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 06/10/2020] [Accepted: 10/02/2020] [Indexed: 11/04/2022] Open
Abstract
Background and purpose Diabetes mellitus is a disorder accompanied by oxidative and inflammatory responses, that might exacerbate vascular complications. The purpose of this study was to investigate the potential antioxidant and anti-inflammatory effects of melatonin (MLN) on streptozotocin (STZ)-induced diabetic rats subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/Re). Experimental approach Diabetes was induced in rats by a single injection of STZ (55 mg/kg; i.p.). The cerebral injury was then induced by MCAO/Re after six weeks. After 24 h of MCAO/Re the MLN (10 mg/kg) was administered orally for 14 days. Serum and tissue samples were extracted to determine malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-1β (IL-1β), and the tumor necrosis factor- α (TNF-α). Part of the brain tissue was kept in formalin for pathological and immunohistochemical studies to determine nuclear factor kappa B (NF-kB) and cyclooxygenase-2 (COX-2) immune reactivity. Findings/Results MCAO/Re in STZ-induced hyperglycaemic rats caused a decrease in brain GSH, an increase in brain MDA, and NO was increased in both serum and brain tissue. Rats showed a prominent increase in the serum and brain inflammatory markers viz. IL-1β and TNF-α. Oral treatment with MLN (10 mg/kg) for two weeks reduced the brain levels of MDA, NO, IL-1β, and TNF-α. Impressive amelioration in pathological findings, as well as a significant decrease in NF-kB and COX2 immune stained cells of the cerebral cortex, hippocampus, and cerebellum, occurred after treatment with MLN. It also succeeded to suppress the exacerbation of damage in the brain of hyperglycaemic rats. Conclusion and implications Daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state.
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Affiliation(s)
- Dalia O Saleh
- Pharmacology Department, National Research Centre, Dokki, Giza, Egypt
| | | | - Sally W Al-Awdan
- Pharmacology Department, National Research Centre, Dokki, Giza, Egypt
| | - Azza Hassan
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Gihan F Asaad
- Pharmacology Department, National Research Centre, Dokki, Giza, Egypt
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15
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Promsan S, Lungkaphin A. The roles of melatonin on kidney injury in obese and diabetic conditions. Biofactors 2020; 46:531-549. [PMID: 32449276 DOI: 10.1002/biof.1637] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 04/24/2020] [Indexed: 01/07/2023]
Abstract
Obesity is a common and complex health problem worldwide and can induce the development of Type 2 diabetes. Chronic kidney disease (CKD) is a complication occurring as a result of obesity and diabetic conditions that lead to an increased mortality rate. There are several mechanisms and pathways contributing to kidney injury in obese and diabetic conditions. The expansion of adipocytes triggers proinflammatory cytokines release into blood circulation and bind with the receptors at the cell membranes of renal tissues leading to kidney injury. Obesity-mediated inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction are the important causes and progression of CKD. Melatonin (N-acetyl-5-methoxytryptamine) is a neuronal hormone that is synthesized by the pineal gland and plays an essential role in regulating several physiological functions in the human body. Moreover, melatonin has pleiotropic effects such as antioxidant, anti-inflammation, antiapoptosis. In this review, the relationship between obesity, diabetic condition, and kidney injury and the renoprotective effect of melatonin in obese and diabetic conditions from in vitro and in vivo studies have been summarized and discussed.
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MESH Headings
- Adipocytes/drug effects
- Adipocytes/metabolism
- Adipocytes/pathology
- Adipose Tissue/drug effects
- Adipose Tissue/metabolism
- Adipose Tissue/pathology
- Animals
- Anti-Inflammatory Agents/metabolism
- Anti-Inflammatory Agents/pharmacology
- Antioxidants/metabolism
- Antioxidants/pharmacology
- Apoptosis/drug effects
- Cytokines/metabolism
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/genetics
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/pathology
- Epithelial Cells/drug effects
- Epithelial Cells/metabolism
- Epithelial Cells/pathology
- Humans
- Kidney/drug effects
- Kidney/metabolism
- Kidney/pathology
- Melatonin/metabolism
- Melatonin/pharmacology
- Obesity/drug therapy
- Obesity/genetics
- Obesity/metabolism
- Obesity/pathology
- Oxidative Stress/drug effects
- Protective Agents/metabolism
- Protective Agents/pharmacology
- Receptors, Cytokine/genetics
- Receptors, Cytokine/metabolism
- Renal Insufficiency, Chronic/genetics
- Renal Insufficiency, Chronic/metabolism
- Renal Insufficiency, Chronic/pathology
- Renal Insufficiency, Chronic/prevention & control
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Affiliation(s)
- Sasivimon Promsan
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Anusorn Lungkaphin
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center for Research and Development of Natural Products for Health, Chiang Mai University Chiang Mai, Thailand
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16
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Sahan A, Akbal C, Tavukcu HH, Cevik O, Cetinel S, Sekerci CA, Sener TE, Sener G, Tanidir Y. Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression. Andrologia 2020; 52:e13639. [PMID: 32478903 DOI: 10.1111/and.13639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/29/2020] [Accepted: 04/19/2020] [Indexed: 11/28/2022] Open
Abstract
A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg-1 day-1 ) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury.
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Affiliation(s)
- Ahmet Sahan
- Department of Urology, Kartal Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey
| | - Cem Akbal
- Department of Urology, School of Medicine, Acibadem University, Istanbul, Turkey
| | - Hasan Huseyin Tavukcu
- Department of Urology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
| | - Ozge Cevik
- Department of Biochemistry, School of Medicine, Adnan Menderes University, Aydın, Turkey
| | - Sule Cetinel
- Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Cagrı Akın Sekerci
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Tarik Emre Sener
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Goksel Sener
- Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey
| | - Yiloren Tanidir
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
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17
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Song YJ, Zhong CB, Wu W. Cardioprotective effects of melatonin: Focusing on its roles against diabetic cardiomyopathy. Biomed Pharmacother 2020; 128:110260. [PMID: 32447213 DOI: 10.1016/j.biopha.2020.110260] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/01/2020] [Accepted: 05/10/2020] [Indexed: 02/06/2023] Open
Abstract
Melatonin is a pineal-produced indole known for its anti-aging, antiapoptotic and antioxidant properties. In past decades, the protective potentials of melatonin for cardiovascular diseases, such as atherosclerosis and myocardial infarction, have been widely revealed, triggering more investigations focused on other cardioprotective effects of melatonin. Recently, the roles of melatonin in diabetic cardiomyopathy (DCM) have attracted increased attention. In this regard, researchers found that melatonin attenuated cardiac fibrosis and hypertrophy, thus interrupting the development of DCM. Retinoid-related orphan receptor α is a key melatonin receptor that contributed to the cardioprotective effect of melatonin in hearts with DCM. For the downstream mechanisms, the inhibition of mammalian STE20-like kinase 1 plays a pivotal role, which exerts antiapoptotic and proautophagic effects, thus enhancing cardiac tolerance in high-glucose conditions. In addition, other signalling mechanisms, such as sirtuin-1/peroxisome proliferator-activated receptor gamma-coactivator alpha and endoplasmic reticulum-related signalling, are also involved in the protective effects of melatonin on cardiomyocytes under diabetic conditions. This review will focus on the protective signalling mechanisms regulated by melatonin and provide a better understanding of the therapeutic applications of melatonin signalling in DCM.
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Affiliation(s)
- Yan-Jun Song
- Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, 1 Shuai Fu Yuan, Beijing, 100730, PR China.
| | - Chong-Bin Zhong
- Department of Cardiology, Heart Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, PR China.
| | - Wei Wu
- Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, 1 Shuai Fu Yuan, Beijing, 100730, PR China.
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18
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Pourhanifeh MH, Hosseinzadeh A, Dehdashtian E, Hemati K, Mehrzadi S. Melatonin: new insights on its therapeutic properties in diabetic complications. Diabetol Metab Syndr 2020; 12:30. [PMID: 32280378 PMCID: PMC7140344 DOI: 10.1186/s13098-020-00537-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 03/27/2020] [Indexed: 12/11/2022] Open
Abstract
Diabetes and diabetic complications are considered as leading causes of both morbidity and mortality in the world. Unfortunately, routine medical treatments used for affected patients possess undesirable side effects, including kidney and liver damages as well as gastrointestinal adverse reactions. Therefore, exploring the novel therapeutic strategies for diabetic patients is a crucial issue. It has been recently shown that melatonin, as main product of the pineal gland, despite its various pharmacological features including anticancer, anti-aging, antioxidant and anti-inflammatory effects, exerts anti-diabetic properties through regulating various cellular mechanisms. The aim of the present review is to describe potential roles of melatonin in the treatment of diabetes and its complications.
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Affiliation(s)
| | - Azam Hosseinzadeh
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ehsan Dehdashtian
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Karim Hemati
- Department of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran
| | - Saeed Mehrzadi
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
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19
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Onaolapo AY, Adebisi EO, Adeleye AE, Olofinnade AT, Onaolapo OJ. Dietary Melatonin Protects Against Behavioural, Metabolic, Oxidative, and Organ Morphological Changes in Mice that are Fed High-Fat, High- Sugar Diet. Endocr Metab Immune Disord Drug Targets 2020; 20:570-583. [PMID: 32138638 DOI: 10.2174/1871530319666191009161228] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 08/19/2019] [Accepted: 08/19/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Metabolic syndrome is a complex pattern of disorders that occur jointly and is associated with an increased risk of cardiovascular and cerebrovascular disease. Therefore the need for more-efficient options of treatment has become imperative. OBJECTIVE This study examined the effect of dietary-melatonin in the management of behavioural, metabolic, antioxidant, and organ changes due to high-fat/high-sugar (HFHS) diet-induced metabolic syndrome in mice. METHODS Mice were randomly assigned into five groups of ten animals each. Groups were normal control [fed standard diet (SD)], HFHS control, and 3 groups of melatonin incorporated into HFHS at 2.5, 5, and 10 mg/kg of feed. Mice were fed for seven weeks, and body weight was assessed weekly. Open-field behaviours, radial-arm, and Y-maze spatial memory were scored at the end of the experimental period. Twenty-four hours after the last behavioural test, blood was taken for estimation of blood glucose levels after an overnight fast. Animals were then euthanised, and blood was taken for estimation of plasma insulin, leptin, and adiponectin levels, and serum lipid profile. The liver, kidneys, and brain were excised and processed for general histology, while homogenates of the liver and whole brain were used to assess oxidative stress parameters. RESULTS Results showed that dietary melatonin (compared to HFHS diet) was associated with a decrease in body weight, food intake, and novelty-induced behaviours; and an increase in spatial-working memory scores. A decrease in glucose, insulin, leptin, and malondialdehyde levels; and an increase in adiponectin levels and superoxide dismutase activity were also observed. Histomorphological/ histomorphometric examination revealed evidence of organ injury with HFHS diet, and varying degrees of amelioration with melatonin-supplemented diet. CONCLUSION In conclusion, dietary melatonin supplementation may have beneficial effects in the management of the metabolic syndrome.
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Affiliation(s)
- Adejoke Yetunde Onaolapo
- Behavioural Neuroscience and Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria.,Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria
| | | | | | - Anthony Tope Olofinnade
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, College of Medicine, Lagos State University, Ikeja, Lagos State, Nigeria
| | - Olakunle James Onaolapo
- Behavioural Neuroscience and Neuropharmacology Unit, Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria
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20
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Espino J, Rodríguez AB, Pariente JA. Melatonin and Oxidative Stress in the Diabetic State: Clinical Implications and Potential Therapeutic Applications. Curr Med Chem 2019; 26:4178-4190. [PMID: 29637854 DOI: 10.2174/0929867325666180410094149] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 12/07/2017] [Accepted: 12/07/2017] [Indexed: 02/07/2023]
Abstract
All living organisms exhibit circadian rhythms, which govern the majority of biological functions, including metabolic processes. Misalignment of these circadian rhythms increases the risk of developing metabolic diseases. Thus, disruption of the circadian system has been proven to affect the onset of type 2 diabetes mellitus (T2DM). In this context, the pineal indoleamine melatonin is a signaling molecule able to entrain circadian rhythms. There is mounting evidence that suggests a link between disturbances in melatonin production and impaired insulin, glucose, lipid metabolism, and antioxidant capacity. Besides, several genetic association studies have causally associated various single nucleotide polymorphysms (SNPs) of the human MT2 receptor with increased risk of developing T2DM. Taken together, these data suggest that endogenous as well as exogenous melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion but also by providing protection against reactive oxygen species (ROS) since pancreatic β-cells are very susceptible to oxidative stress due to their low antioxidant capacity.
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Affiliation(s)
- Javier Espino
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
| | - Ana B Rodríguez
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
| | - José A Pariente
- Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain
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21
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Ahmad Hajam Y, Rai S, Basheer M, Ghosh H, Singh S. Protective Role of Melatonin in Streptozotocin Induced Pancreatic Damages in Diabetic Wistar Rat. Pak J Biol Sci 2019; 21:423-431. [PMID: 30724043 DOI: 10.3923/pjbs.2018.423.431] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Hyperglycemia is a representative hallmark and risk factor for diabetes and is closely linked to diabetes associated complications. The aim of the present study was to evaluate the therapeutic potential of exogenous melatonin against the streptozotocin induced pancreatic damages in rats. MATERIALS AND METHODS Streptozotocin was injected for consecutive 6 days. Diabetes was confirmed by blood glucose measurement after 72 h and on 7th day after injection. Animals having blood glucose level above 250 mg dL-1 were considered as diabetic and were administered exogenous melatonin for 4 weeks. Animals were euthanized after last dose, pancreas were dissected out, weighed and fixed in Bouin's fixative for histology and further tissues were kept at -20°C for biochemistry. RESULTS Diabetic rats displayed significant increase in lipid peroxidation, but pancreatic weight index, antioxidant system (GSH, SOD and CAT) showed decrease. Melatonin treatment to diabetic rats restored the alteration in physiological and biochemical markers. Results were supported by the histopathological observations, STZ treated pancreas showed damage in islets of langerhans, while as melatonin treated diabetic rats recovered the cellular architecture which inturn normalize the function of the pancreas. CONCLUSION Therefore, melatonin might be considered as a molecule to protect the pancreatic damages.
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22
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Gurel-Gokmen B, Ipekci H, Oktay S, Alev B, Ustundag UV, Ak E, Akakın D, Sener G, Emekli-Alturfan E, Yarat A, Tunali-Akbay T. Melatonin improves hyperglycemia induced damages in rat brain. Diabetes Metab Res Rev 2018; 34:e3060. [PMID: 30098300 DOI: 10.1002/dmrr.3060] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 06/14/2018] [Accepted: 07/30/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Diabetes mellitus is an endocrine disorder which is characterized by the development of resistance to the cellular activity of insulin or inadequate insulin production. It leads to hyperglycemia, prolonged inflammation, and oxidative stress. Oxidative stress is assumed to play an important role in the development of diabetic complications. Melatonin is the hormone that interacts with insulin in diabetes. Therefore, in this study, the effects of melatonin treatment with or without insulin were examined in diabetic rat brain. METHODS Rats were divided into five groups as control, diabetes, diabetes + insulin, diabetes + melatonin, and diabetes + melatonin + insulin. Experimental diabetes was induced by streptozotocin (60 mg/kg, i.p.). Twelve weeks after diabetes induction, rats were decapitated. Malondialdehyde, glutathione, sialic acid and nitric oxide levels, superoxide dismutase, catalase, glutathione-S-transferase, myeloperoxidase, and tissue factor activities were determined in brain tissue. RESULTS Melatonin alone showed its antioxidant effect by increasing brain glutathione level, superoxide dismutase, catalase, and glutathione-S-transferase activities and decreasing malondialdehyde level in experimental diabetes. Although insulin did not have a significant effect on glutathione and glutathione-S-transferase, its effects on lipid peroxidation, superoxide dismutase, and catalase were similar to melatonin; insulin also decreased myolopeoxidase activity and increased tissue factor activity. Combined melatonin and insulin treatment mimicked the effects of insulin. CONCLUSION Addition of melatonin to the insulin treatment did not change the effects of insulin, but the detailed role of melatonin alone in the treatment of diabetes merits further experimental and clinical investigation.
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Affiliation(s)
- Begum Gurel-Gokmen
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Hazal Ipekci
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Sehkar Oktay
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Burcın Alev
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Unsal Velı Ustundag
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Esın Ak
- Basic Medical Sciences, Histology and Embryology, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Dılek Akakın
- Basic Medical Sciences, Histology and Embryology, Marmara University, Faculty of Medicine, Istanbul, Turkey
| | - Goksel Sener
- Pharmacology, Marmara University, Faculty of Pharmacy, Istanbul, Turkey
| | - Ebru Emekli-Alturfan
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Aysen Yarat
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
| | - Tugba Tunali-Akbay
- Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey
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Characterization and Attenuation of Streptozotocin-Induced Diabetic Organ Damage by Polysaccharides from Spent Mushroom Substrate (Pleurotus eryngii). OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:4285161. [PMID: 30364025 PMCID: PMC6186375 DOI: 10.1155/2018/4285161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 07/19/2018] [Indexed: 01/28/2023]
Abstract
The aim of this work was to characterize spent mushroom substrate polysaccharides (MSP) from Pleurotus eryngii and their antioxidant and organ protective effects in streptozotocin- (STZ-) induced diabetic mice. The enzymatic-, acidic-, and alkalic- (En-, Ac-, and Al-) MSP were extracted from P. eryngii with snailase (4%), hydrochloric acid (1 mol/l), and sodium hydroxide (1 mol/l), respectively. The characterizations were evaluated by spectral analysis. In animal experiments, the enzymatic activities, lipid peroxide contents, and serum lipid parameters were measured, and histological observations of the liver, kidney, pancreas, and heart were conducted. The results demonstrated that treatment with En-, Ac-, and Al-MSP increased the organ enzymatic activities, decreased the organ lipid peroxide contents, mitigated the serum biochemistry values, and ameliorated the histopathology of diabetic mice, indicating that En-, Ac-, and Al-MSP could potentially be used as functional foods for the prevention of diabetes.
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Hadjzadeh M, Alikhani V, Hosseinian S, Zarei B, Keshavarzi Z. THE EFFECT OF MELATONIN AGAINST GASTRIC OXIDATIVE STRESS AND DYSLIPIDEMIA IN STREPTOZOTOCIN-INDUCED DIABETIC RATS. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2018; 14:453-458. [PMID: 31149296 PMCID: PMC6516406 DOI: 10.4183/aeb.2018.453] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate the possible protective effects of MT against gastric oxidative stress and dyslipidemia in streptozotocin (STZ) - induced diabetic rats. METHODS Forty male Wistar rats were randomly divided into five groups: control, diabetic, MT 5 mg/kg+ STZ, MT 10 mg/kg+ STZ and MT 20 mg/kg+ STZ. STZ (60 mg/kg) was intraperitoneally (ip) injected as a single dose for diabetes induction. One week after STZ administration, MT was injected daily as ip for 14 days. The levels of malondialdehyde (MDA), total thiol and glutathione, as well as superoxide dismutase (SOD) and catalase activities were measured in gastric tissue. Serum concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were also determined. RESULTS Serum glucose significantly increased in diabetic group compared to control group. STZ induced a significant decrease in gastric tissue levels of total thiol, glutathione, catalase and SOD activities and a significant increase in MDA concentration. In diabetic rats, serum TG, LDL and TC were significantly higher and HDL was significantly lower than in the control group. Treatment of diabetic rats with MT caused a significant increase in gastric total thiol content and glutathione concentration as well as SOD and catalase activities. Gastric MDA concentration and serum LDL, TG and TC were significantly lower in MT-treated groups when compared with diabetic group. CONCLUSION These data suggested that MT has a therapeutic effect on gastric oxidative damage and dyslipidemia induced by diabetes that possibly may be due to its antioxidant effects.
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Affiliation(s)
- M.A.R. Hadjzadeh
- Mashhad University of Medical Sciences, School of Medicine, Department of physiology, Bojnurd, Iran
- Mashhad University of Medical Sciences, Psychiatry and Behavioral Sciences Research Center, Division of Neurocognitive Sciences, Bojnurd, Iran
| | - V. Alikhani
- Mashhad University of Medical Sciences, School of Medicine, Department of physiology, Bojnurd, Iran
| | - S. Hosseinian
- Mashhad University of Medical Sciences, School of Medicine, Department of physiology, Bojnurd, Iran
- Mashhad University of Medical Sciences, Neurogenic Inflammation Research Center, Mashhad, Bojnurd, Iran
| | - B. Zarei
- Mashhad University of Medical Sciences, School of Medicine, Department of physiology, Bojnurd, Iran
| | - Z. Keshavarzi
- Mashhad University of Medical Sciences, North Khorasan University of Medical Sciences, Natural Products and Medicinal Plants Research Center, Bojnurd, Iran
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Bozkurt A, Karabakan M, Aktas BK, Gunay M, Keskin E, Hirik E. Low serum melatonin levels are associated with erectile dysfunction. Int Braz J Urol 2018; 44:794-799. [PMID: 29757573 PMCID: PMC6092660 DOI: 10.1590/s1677-5538.ibju.2017.0663] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 04/08/2018] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Melatonin is a hormone secreted from the pineal gland and has anti-oxidative and anti-inflammatory effects. Oxidative stress is considered as an important factor in the etiology of erectile dysfunction (ED), and in many experimental models, positive results have been obtained with melatonin treatment. This study aimed to measure serum melatonin levels in ED patients and to investigate the possible relationship between ED and melatonin levels. MATERIALS AND METHODS Sixty-two patients diagnosed with mild, moderate or severe ED according to the five-item International Erectile Function Index (IIEF-5) and 22 healthy individuals were included in the study. The serum melatonin levels, anthropometric data, and other biochemical and hormonal parameters of all the subjects were recorded. Detailed anamnesis was also obtained in terms of diabetes, hypertension, cardiovascular diseases, smoking status, and alcohol use. RESULTS The serum melatonin level was found 34.2±13.3 ng/dL in the mild ED group, 33.3±14.7 ng/dL in the moderate ED group, 34.8±17.2 ng/dL in the severe ED group, and 44.6±16.5 ng/dL in the control group. The serum melatonin levels were significantly lower in all ED groups compared to the control group (p=0.019). There was no significant difference in the serum melatonin levels between the three ED groups. Diabetes, hypertension, cardiovascular diseases, smoking and alcohol use were not significantly different between the ED groups (p>0.05). CONCLUSION We consider that if our findings are supported by further studies with larger populations, the measurement of the serum melatonin level may have a future role in the diagnosis and treatment of ED.
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Affiliation(s)
- Aliseydi Bozkurt
- Department of Urology, Erzincan University Mengucek Gazi Research and Training Hospital, Erzincan, Turkey
| | - Mehmet Karabakan
- Department of Urology, Mersin Toros State Hospital, Mersin, Turkey
| | - Binhan Kagan Aktas
- Department of Urology, Ankara Numune Research and Training Hospital, Ankara, Turkey
| | - Murat Gunay
- Department of Clinical Biochemistry, Erzincan University Mengucek Gazi Research and Training Hospital, Erzincan, Turkey
| | - Ercüment Keskin
- Department of Urology, Erzincan University Mengucek Gazi Research and Training Hospital, Erzincan, Turkey
| | - Erkan Hirik
- Department of Urology, Erzincan University Mengucek Gazi Research and Training Hospital, Erzincan, Turkey
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Joshi A, Lad H, Sharma H, Bhatnagar D. Evaluation of phytochemical composition and antioxidative, hypoglycaemic and hypolipidaemic properties of methanolic extract of Hemidesmus indicus roots in streptozotocin-induced diabetic mice. CLINICAL PHYTOSCIENCE 2018. [DOI: 10.1186/s40816-018-0064-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Madhuri K, Naik PR. Ameliorative effect of borneol, a natural bicyclic monoterpene against hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic Wistar rats. Biomed Pharmacother 2017; 96:336-347. [DOI: 10.1016/j.biopha.2017.09.122] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 09/19/2017] [Accepted: 09/23/2017] [Indexed: 11/15/2022] Open
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Effects of Melatonin on Glucose Homeostasis, Antioxidant Ability, and Adipokine Secretion in ICR Mice with NA/STZ-Induced Hyperglycemia. Nutrients 2017; 9:nu9111187. [PMID: 29109369 PMCID: PMC5707659 DOI: 10.3390/nu9111187] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/04/2017] [Accepted: 10/26/2017] [Indexed: 01/04/2023] Open
Abstract
Diabetes is often associated with decreased melatonin level. The aim was to investigate the effects of different dosage of melatonin on glucose hemostasis, antioxidant ability and adipokines secretion in diabetic institute for cancer research (ICR) mice. Forty animals were randomly divided into five groups including control (C), diabetic (D), low-dosage (L), medium-dosage (M), and high-dosage (H) groups. Groups L, M, and H, respectively, received oral melatonin at 10, 20, and 50 mg/kg of BW (body weight) daily after inducing hyperglycemia by nicotinamide (NA)/ streptozotocin (STZ). After the six-week intervention, results showed that melatonin administration increased insulin level and performed lower area under the curve (AUC) in H group (p < 0.05). Melatonin could lower hepatic Malondialdehyde (MDA) level in all melatonin-treated groups and increase superoxide dismutase activity in H group (p < 0.05). Melatonin-treated groups revealed significant higher adiponectin in L group, and lower leptin/adiponectin ratio and leptin in M and H groups (p < 0.05). Melatonin could lower cholesterol and triglyceride in liver and decrease plasma cholesterol and low-density lipoprotein-cholesterol (LDL-C) in L group, and increase plasma high-density lipoprotein-cholesterol (HDL-C) in H group (p < 0.05). Above all, melatonin could decrease oxidative stress, increase the adiponectin level and improve dyslipidemia, especially in H group. These data support melatonin possibly being a helpful aid for treating hyperglycemia-related symptoms.
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Yeh YT, Chiang AN, Hsieh SC. Chinese Olive (Canarium album L.) Fruit Extract Attenuates Metabolic Dysfunction in Diabetic Rats. Nutrients 2017; 9:nu9101123. [PMID: 29036927 PMCID: PMC5691739 DOI: 10.3390/nu9101123] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 10/11/2017] [Accepted: 10/12/2017] [Indexed: 02/06/2023] Open
Abstract
Hyperglycemia and dysregulation of lipid metabolism play a crucial role in metabolic dysfunction. The aims of present study were to evaluate the ameliorative effect of the ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc) on high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. CO-EtOAc, rich in gallic acid and ellagic acid, could markedly decreased the body weight and epididymal adipose mass. In addition, CO-EtOAc increased serum HDL-C levels, hepatic GSH levels, and antioxidant enzyme activities; lowered blood glucose, serum levels of total cholesterol (TC), triglycerides (TG), bile acid, and tumor necrosis factor alpha (TNFα); and reduced TC and TG in liver. We further demonstrated that CO-EtOAc mildly suppressed hepatic levels of phosphorylated IRS-1, TNF-α, and IL-6, but enhanced Akt phosphorylation. The possible mechanisms of cholesterol metabolism were assessed by determining the expression of genes involved in cholesterol transportation, biosynthesis, and degradation. It was found that CO-EtOAc not only inhibited mRNA levels of SREBP-2, HMG-CoAR, SR-B1, and CYP7A1 but also increased the expression of genes, such as ABCA1 and LDLR that governed cholesterol efflux and cholesterol uptake. Moreover, the protein expressions of ABCA1 and LDLR were also significantly increased in the liver of rats supplemented with CO-EtOAc. We suggest that Chinese olive fruit may ameliorate metabolic dysfunction in diabetic rats under HFD challenge.
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Affiliation(s)
- Yu-Te Yeh
- Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan.
| | - An-Na Chiang
- Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
| | - Shu-Chen Hsieh
- Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan.
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Zhang C, Li J, Hu C, Wang J, Zhang J, Ren Z, Song X, Jia L. Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice. Sci Rep 2017; 7:10847. [PMID: 28883631 PMCID: PMC5589823 DOI: 10.1038/s41598-017-11457-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 08/24/2017] [Indexed: 02/06/2023] Open
Abstract
The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH2, -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.
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Affiliation(s)
- Chen Zhang
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Juan Li
- Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Chunlong Hu
- College of Forestry, Shandong Agricultural University, Taian, 271018, China
| | - Jing Wang
- The Central Hospital of Taian, Taian, 271000, China
| | - Jianjun Zhang
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Zhenzhen Ren
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Xinling Song
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Le Jia
- College of Life Science, Shandong Agricultural University, Taian, 271018, China.
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Rebai R, Jasmin L, Boudah A. The antidepressant effect of melatonin and fluoxetine in diabetic rats is associated with a reduction of the oxidative stress in the prefrontal and hippocampal cortices. Brain Res Bull 2017; 134:142-150. [PMID: 28746841 DOI: 10.1016/j.brainresbull.2017.07.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 07/10/2017] [Accepted: 07/19/2017] [Indexed: 12/16/2022]
Abstract
In the past few years possible mechanisms that link diabetes and depression have been found. One of these mechanisms is the increase in lipid peroxidation and decrease in antioxidant activity in the hippocampal and prefrontal cortices, which are brain areas involved in mood. The goal of the present study was to evaluate the effect of an antidepressant and of an antioxidant on behavior and oxidative activity in brains of diabetic rats. Rats rendered diabetic after a treatment with streptozotocin (STZ) (60mg/kg) were treated with fluoxetine (15mg/kg), melatonin (10mg/kg), or vehicle for 4 weeks. All animals were tested for signs of depression and anxiety using the elevated plus maze (EPM), open field test (OFT) and the forced swim test (FST). Four groups were compared: (1) normoglycemic, (2) hyperglycemic vehicle treated, and hyperglycemic (3) fluoxetine or (4) melatonin treated rats. On the last day of the study, blood samples were obtained to determine the levels of hemoglobin A1c (HbA1c). Also, brain samples were collected to measure the oxidative stress in the hippocampal and prefrontal cortices using the thiobarbituric acid reactive substances (TBARS) assay. The activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were also measured on the brain samples. The results show that both fluoxetine and melatonin decrease the signs of depression and anxiety in all tests. Concomitantly, the levels of HbA1c were reduced in drug treated rats, and to a greater degree in the fluoxetine group. In the cerebral cortex of diabetic rats, TBARS was increased, while the activity of CAT, GPx and GST were decreased. Fluoxetine and melatonin treatments decreased TBARS in both cortices. In the prefrontal cortex, fluoxetine and melatonin restored the activity of CAT, while only melatonin improved the activity of GPx and GST. In the hippocampus, the activity of GPx alone was restored by melatonin, while fluoxetine had no effect. These results suggest that antidepressants and antioxidants can counter the mood and oxidative disorders associated with diabetes. While these effects could result from a decreased production of reactive oxygen species (ROS) remains to be established.
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Affiliation(s)
- Redouane Rebai
- Department of Biochemistry & Molecular and Cellular Biology, Faculty of Natural and Life Sciences, University of Mentouri Brothers, Constantine BP, 325 Road of Ain El Bey, 25017 Constantine, Algeria.
| | - Luc Jasmin
- Department of Oral and Maxillofacial Surgery, University of California, 521 Parnassus Ave, Campus Box 0440, San Francisco, CA 94143, USA.
| | - Abdennacer Boudah
- National Higher School of Biotechnology, Ville universitaire Ali Mendjeli, BP E66 25100 Constantine, Algeria.
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Balbaa M, Abdulmalek SA, Khalil S. Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs. PLoS One 2017; 12:e0172429. [PMID: 28505155 PMCID: PMC5432169 DOI: 10.1371/journal.pone.0172429] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 02/03/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated. METHODS T2DM-induced rats were orally and daily administrated 2.0 ml NSO, 100 mg metformin (MT), 0.8 mg glimepiride (GI) and different combinations (100 mg MT & 2.0 ml NSO, 0.8 mg GI & 2.0 ml NSO and 2.0 ml NSO & intraperitoneal injection of 1/100 LD50 of IOMe-AG538) per kg body weight for 21 days. RESULTS A significant increase in the brain lipid peroxidation and decrease in the antioxidant status with peripheral and central production of pro-inflammatory mediators were observed in diabetes-induced rats. The brain AChE was activated and associated with diminished brain glucose level and cholinergic function. In addition, the brain insulin resistance and the attenuated insulin signaling pathway (p-IRS/ p-AKT/p-GSK-3β) were accompanied by an augmentation in GSK-3β level, which in turn may contribute in the extensive alterations of Tau phosphorylation along with changes in PP2A level. Furthermore, neuronal loss and elevation in Aβ-42 plaque formation were observed due to a low IDE formation and an increased expression of p53, BACE1 and APP with diminished ADAM10, SIRT1 and BDNF levels. The expression profile of AD-related miRNAs in sera and brain tissues displayed its neuro-protection role. The treatment of diabetes-induced rats with NSO and the anti-diabetic drugs alone and/or in combination have the potential to suppress the oxidative stress, the pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin-signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque formation and Tau hyper-phosphorylation and restores AD-related miRNA normal levels. CONCLUSION These data suggest that NSO or its combined treatments with anti-diabetic drugs have a possible benefit as disease modifying agents for the insulin resistance in the brain through enhancing brain insulin signaling pathway.
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Affiliation(s)
- Mahmoud Balbaa
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Shaymaa A. Abdulmalek
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Sofia Khalil
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
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Zhao Y, Xu L, Ding S, Lin N, Ji Q, Gao L, Su Y, He B, Pu J. Novel protective role of the circadian nuclear receptor retinoic acid-related orphan receptor-α in diabetic cardiomyopathy. J Pineal Res 2017; 62. [PMID: 27862268 DOI: 10.1111/jpi.12378] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 11/15/2016] [Indexed: 12/11/2022]
Abstract
Diabetic cardiomyopathy is a major complication that significantly contributes to morbidity and mortality in diabetics with few therapies. Moreover, antidiabetic drugs reported inconsistent or even adverse cardiovascular effects, suggesting that it is important to exploit novel therapeutic targets against diabetic cardiomyopathy. Here, we observed that the nuclear melatonin receptor, the retinoic acid-related orphan receptor-α (RORα), was downregulated in diabetic hearts. By utilizing a mouse line with RORα disruption, we demonstrated that RORα deficiency led to significantly augmented diastolic dysfunction and cardiac remodeling induced by diabetes. Microscopic and molecular analyses further indicated that the detrimental effects of RORα deficiency were associated with aggravated myocardial apoptosis, autophagy dysfunction, and oxidative stress by disrupting antioxidant gene expression. By contrast, restoration of cardiac RORα levels in transgenic mice significantly improved cardiac functional and structural parameters at 8 weeks after diabetes induction. Consistent with genetic manipulation, pharmacological activation of RORα by melatonin and SR1078 (a synthetic agonist) showed beneficial effects against diabetic cardiomyopathy, while the RORα inhibitor SR3335 significantly exacerbated cardiac impairments in diabetic mice. Collectively, these findings suggest that cardiac-targeted manipulation of nuclear melatonin receptor RORα may hold promise for delaying diabetic cardiomyopathy development.
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MESH Headings
- Animals
- Apoptosis/drug effects
- Apoptosis/genetics
- Autophagy/drug effects
- Autophagy/genetics
- Benzamides/pharmacology
- Diabetic Cardiomyopathies/drug therapy
- Diabetic Cardiomyopathies/genetics
- Diabetic Cardiomyopathies/metabolism
- Diabetic Cardiomyopathies/pathology
- Mice
- Mice, Mutant Strains
- Myocardium/metabolism
- Myocardium/pathology
- Nuclear Receptor Subfamily 1, Group F, Member 1/agonists
- Nuclear Receptor Subfamily 1, Group F, Member 1/antagonists & inhibitors
- Nuclear Receptor Subfamily 1, Group F, Member 1/genetics
- Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism
- Oxidative Stress/drug effects
- Oxidative Stress/genetics
- Receptors, Melatonin/genetics
- Receptors, Melatonin/metabolism
- Sulfonamides/pharmacology
- Thiophenes/pharmacology
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Affiliation(s)
- Yichao Zhao
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Longwei Xu
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Song Ding
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Nan Lin
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qingqi Ji
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lingchen Gao
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuanyuan Su
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ben He
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jun Pu
- Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Ekin S, Arısoy A, Gunbatar H, Sertogullarindan B, Sunnetcioglu A, Sezen H, Asker S, Yıldız H. The relationships among the levels of oxidative and antioxidative parameters, FEV1 and prolidase activity in COPD. Redox Rep 2017; 22:74-77. [PMID: 26870880 PMCID: PMC6837489 DOI: 10.1080/13510002.2016.1139293] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
INTRODUCTION Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by poorly reversible airflow limitations associated with an abnormal inflammatory response of the lung. METHODS We investigated whether prolidase levels in serum, total antioxidant status, total oxidative status (TOS), and the oxidative stress index (OSI) were associated with the etiopathogenesis of COPD, and whether there is a relationship between prolidase activity and oxidative parameters and carotid artery intima-media thickness (CIMT) in patients with COPD. This study included 91 patients with COPD and 15 control cases. Routine haematological and biochemical parameters were determined in all patients. All subjects were fully informed about the study and provided consent. RESULTS The mean age of the patients with COPD was 61.3 ± 10.5 years and that of the control group was 56.2 ± 12.1 years. The control group had a significantly higher plasma prolidase level than that in the COPD group. TOS and OSI levels in the control group were significantly lower than those in the COPD group. However, no significant differences were found in TALs or CIMT levels between the COPD and control groups. A negative correlation was detected between prolidase activity and age; however, no significant difference in age was observed between the two groups. CONCLUSION These results indicate that prolidase activity decreases in patients with COPD.
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Affiliation(s)
- Selami Ekin
- Yuzuncu Yıl University, Pulmonary Medicine, 65080 Van, Turkey
| | - Ahmet Arısoy
- Yuzuncu Yıl University, Pulmonary Medicine, 65080 Van, Turkey
| | - Hulya Gunbatar
- Yuzuncu Yıl University, Pulmonary Medicine, 65080 Van, Turkey
| | | | | | - Hatice Sezen
- Department of Biochemistry, Harran University, Turkey
| | - Selvi Asker
- Yuzuncu Yıl University, Pulmonary Medicine, 65080 Van, Turkey
| | - Hanifi Yıldız
- Private Lokman Hekim Hospital, Pulmonary Medicine, Turkey
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Protective effects on liver, kidney and pancreas of enzymatic- and acidic-hydrolysis of polysaccharides by spent mushroom compost (Hypsizigus marmoreus). Sci Rep 2017; 7:43212. [PMID: 28233836 PMCID: PMC5324114 DOI: 10.1038/srep43212] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 01/20/2017] [Indexed: 12/14/2022] Open
Abstract
The present work investigated the protective effects on liver, kidneys and pancreas of spent mushroom compost polysaccharide (SCP) and its hydrolysates (enzymatic- (ESCP) and acid-hydrolyzed SCP (ASCP)) from Hypsizigus marmoreus, in streptozotocin (STZ)-induced diabetic mice. The results showed that enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) and non-enzymatic activities (total antioxidant capacity (T-AOC)) were significantly increased, the lipid peroxide contents (lipid peroxide (LPO) and malonaldehyde (MDA)) were remarkably reduced, and the clinical parameters were observably mitigated in diabetic mice treated with these three polysaccharides. Furthermore, histological observations also indicated recovery. These conclusions demonstrated that both SCP and its hydrolysates ESCP and ASCP possessed potent antioxidant activities and can be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.
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Yildirimturk S, Batu S, Alatli C, Olgac V, Firat D, Sirin Y. The effects of supplemental melatonin administration on the healing of bone defects in streptozotocin-induced diabetic rats. J Appl Oral Sci 2016; 24:239-49. [PMID: 27383705 PMCID: PMC5022211 DOI: 10.1590/1678-775720150570] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 03/15/2016] [Indexed: 12/31/2022] Open
Abstract
Diabetes mellitus (DM) causes an increased production of free radicals that can impair bone healing. Melatonin is a hormone secreted mainly by the pineal gland, which participates in the neutralization process of free radicals.
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Affiliation(s)
- Senem Yildirimturk
- - Istanbul University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul, Turkey
| | - Sule Batu
- - Istanbul University, Faculty of Dentistry, Department of Biochemistry, Istanbul, Turkey
| | - Canan Alatli
- - Istanbul University, Institute of Oncology, Department of Pathology, Istanbul, Turkey
| | - Vakur Olgac
- - Istanbul University, Institute of Oncology, Department of Pathology, Istanbul, Turkey
| | - Deniz Firat
- - Istanbul University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul, Turkey
| | - Yigit Sirin
- - Istanbul University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul, Turkey
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Lin L, Cui F, Zhang J, Gao X, Zhou M, Xu N, Zhao H, Liu M, Zhang C, Jia L. Antioxidative and renoprotective effects of residue polysaccharides from Flammulina velutipes. Carbohydr Polym 2016; 146:388-95. [PMID: 27112888 DOI: 10.1016/j.carbpol.2016.03.071] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Revised: 03/10/2016] [Accepted: 03/23/2016] [Indexed: 12/20/2022]
Abstract
Three extractable polysaccharides including Ac-RPS, Al-RPS and En-RPS were extracted from the residue of Flammulina velutipes and their antioxidative and renoprotective effects on STZ-induced mice were investigated. Biochemical and antioxidant analysis showed that the En-RPS had potential effects in decreasing the serum levels of CRE, BUN, ALB and GLU significantly, increasing the renal activities of SOD, CAT and GSH-Px remarkably, and reducing the renal contents of MDA prominently. Furthermore, the histopathological observations also displayed that En-RPS could alleviate kidney damage. These results demonstrated that En-RPS extracted from the residue of F. velutipes possessed potent antioxidant activities, and could be used as a promising therapeutic agent for inhibiting the progression of diabetic nephropathy. In addition, the monosaccharide compositions of these three RPS were also analyzed.
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Affiliation(s)
- Lin Lin
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Fangyuan Cui
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Jianjun Zhang
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Xia Gao
- Shandong Agricultural Technology Extending Station, Ji'nan, Shandong 250100, PR China
| | - Meng Zhou
- Quality and Safety Monitoring Center of Animal Products, Ji'nan, Shandong 250002, PR China
| | - Nuo Xu
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Huajie Zhao
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Min Liu
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Chen Zhang
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China
| | - Le Jia
- College of Life Science, Shandong Agricultural University, Taian 271018, PR China.
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Nayki U, Onk D, Balci G, Nayki C, Onk A, Çankaya M, Taskın Kafa AH, Kuzucu M. The effect of melatonin on oxidative stress and apoptosis in experimental diabetes mellitus-related ovarian injury. Gynecol Endocrinol 2016; 32:421-6. [PMID: 26743008 DOI: 10.3109/09513590.2015.1126819] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
We aimed to evaluate the effect of melatonin on oxidative stress and ovarian injury in rats. Twenty-four Sprague-Dawley albino rats were divided into three groups: Group 1 as nondiabetic healthy controls (n = 8), group 2 as nontreated diabetic rats (n = 8) and group 3 as melatonin-treated diabetic rats (n = 8). After overt diabetes was produced by intraperitoneal injection of streptozosin, 20 mg/kg/day of melatonin was given intraperitoneally to group 3 for a week. NF-kB and caspase-3 immunoexpressions, lipid peroxidation, the activities of antioxidative enzymes, total oxidant capacity and total antioxidant capacity were assessed. Immunoexpressions of NF-kB and caspase-3 were significantly lower in group 3 than group 2. There was a significant decrease in superoxide dismutase activity in group 2 than group 1 and a significant increase in group 3 compared with group 2. We observed a nonsignificant decrease in catalase activity between group 1 and group 2 and a nonsignificant increase between group 2 and group 3. There was a nonsignificant increase in the plasma level of total oxidant status in group 2 than group 1, but a significant decrease was observed in group 3 compared to group 2. Total antioxidant status was significantly lower in group 2 compared with group 1 and group 3. In conclusion, melatonin ameliorates the negative effects of oxidative stress on DM-related ovarian injury.
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Affiliation(s)
- Umit Nayki
- a Department of Obstetrics and Gynecology
| | - Didem Onk
- b Department of Anesthesiology and Reanimation
| | | | - Cenk Nayki
- a Department of Obstetrics and Gynecology
| | - Alper Onk
- d Department of Cardiovascular Surgery , and
| | - Murat Çankaya
- e Department of Biochemistry School of Medicine , Erzincan University , Erzincan , Turkey
| | | | - Mehmet Kuzucu
- e Department of Biochemistry School of Medicine , Erzincan University , Erzincan , Turkey
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Effect of Melatonin Intake on Oxidative Stress Biomarkers in Male Reproductive Organs of Rats under Experimental Diabetes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:614579. [PMID: 26064423 PMCID: PMC4438187 DOI: 10.1155/2015/614579] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 04/11/2015] [Accepted: 04/17/2015] [Indexed: 01/01/2023]
Abstract
This study investigated the antioxidant system response of male reproductive organs during early and late phases of diabetes and the influence of melatonin treatment. Melatonin was administered to five-week-old Wistar rats throughout the experiment, in drinking water (10 μg/kg b.w). Diabetes was induced at 13 weeks of age by streptozotocin (4.5 mg/100 g b.w., i.p.) and animals were euthanized with 14 or 21 weeks old. Activities of catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), and lipid peroxidation were evaluated in prostate, testis, and epididymis. The enzymes activities and lipid peroxidation were not affected in testis and epididymis after one or eight weeks of diabetes. Prostate exhibited a 3-fold increase in GPx activity at short-term diabetes and at long-term diabetes there were 2- and 3-fold increase in CAT and GST, respectively (p ≤ 0.01). Melatonin treatment to healthy rats caused a 47% increase in epididymal GPx activity in 14-week-old rats. In prostate, melatonin administration normalized GST activity at both ages and mitigated GPx at short-term and CAT at long-term diabetes. The testis and epididymis were less affected by diabetes than prostate. Furthermore, melatonin normalized the enzymatic disorders in prostate demonstrating its effective antioxidant role, even at low dosages.
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Orman D, Vardi N, Ates B, Taslidere E, Elbe H. Aminoguanidine mitigates apoptosis, testicular seminiferous tubules damage, and oxidative stress in streptozotocin-induced diabetic rats. Tissue Cell 2015; 47:284-90. [PMID: 25862575 DOI: 10.1016/j.tice.2015.03.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Revised: 03/25/2015] [Accepted: 03/25/2015] [Indexed: 02/02/2023]
Abstract
This study aimed to investigate the effect of aminoguanidine (AG) against testicular damage streptozotocin (STZ) induced diabetes. Thirty two rats were separated into four groups: control, AG, STZ and STZ+AG. In the STZ group, 12.5±1.3% of tubules were seen as containing sloughed spermatogenic cells into the lumen, 28.7±1.8% of tubules were atrophic, 46.2±2.1% of tubules were degenerative and 8.5±0.9% of tubules contained giant cells. Statistically, the affected tubule number was significantly lower in the STZ+AG group than in the STZ group. Intensely stained caspase-3 cells showed a statistically significant increase in the STZ group, while it decreased in the STZ+AG group. The enzyme activities of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) level decreased and the level of malondialdehyde (MDA) and nitric oxide (NO) increased in the STZ group, while AG treated diabetic rats showed an increase of CAT, SOD activity and GSH level and a decrease in MDA and NO levels. This study shows that the oxidative stress, increased NO level and apoptotic cell death play an important role in diabetic rat testicular damage and that AG treatment of diabetic rats results in protection of spermatogenic cells against oxidative stress and apoptotic cell death.
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Affiliation(s)
- Dogan Orman
- Inonu University, Faculty of Medicine, Department of Histology and Embryology, Malatya, Turkey
| | - Nigar Vardi
- Inonu University, Faculty of Medicine, Department of Histology and Embryology, Malatya, Turkey
| | - Burhan Ates
- Inonu University, Faculty of Science and Art, Department of Chemistry, Malatya, Turkey
| | - Elif Taslidere
- Inonu University, Faculty of Medicine, Department of Histology and Embryology, Malatya, Turkey
| | - Hulya Elbe
- Mugla Sıtkı Kocman University, Faculty of Medicine, Department of Histology and Embryology, Mugla, Turkey.
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Hossain A, Yamaguchi F, Hirose K, Matsunaga T, Sui L, Hirata Y, Noguchi C, Katagi A, Kamitori K, Dong Y, Tsukamoto I, Tokuda M. Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats. Drug Des Devel Ther 2015; 9:525-35. [PMID: 25632221 PMCID: PMC4304484 DOI: 10.2147/dddt.s71289] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. AIM Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats. METHODS Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. RESULTS d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. CONCLUSION Our findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and hyperglycemia with the preservation of β-cells in the progression of T2DM.
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Affiliation(s)
- Akram Hossain
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
- Research and Development, Matsutani Chemical Industry Co., Ltd., Kitaitami, Itami-Shi, Hyogo, Japan
| | - Fuminori Yamaguchi
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Kayoko Hirose
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Toru Matsunaga
- Division of Hospital Pathology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Li Sui
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Yuko Hirata
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Chisato Noguchi
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Ayako Katagi
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Kazuyo Kamitori
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Youyi Dong
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Ikuko Tsukamoto
- Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
| | - Masaaki Tokuda
- Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan
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Amin AH, El-Missiry MA, Othman AI. Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis. Eur J Pharmacol 2015; 747:166-73. [DOI: 10.1016/j.ejphar.2014.12.002] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 11/30/2014] [Accepted: 12/04/2014] [Indexed: 12/14/2022]
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Elis Yildiz S, Deprem T, Karadag Sari E, Bingol SA, Koral Tasci S, Aslan S, Nur G, Sozmen M. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats. Biotech Histochem 2014; 90:270-7. [PMID: 25539049 DOI: 10.3109/10520295.2014.983548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.
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Akyol S, Ugurcu V, Balci M, Gurel A, Erden G, Cakmak O, Akyol O. Caffeic acid phenethyl ester: its protective role against certain major eye diseases. J Ocul Pharmacol Ther 2014; 30:700-8. [PMID: 25100535 DOI: 10.1089/jop.2014.0046] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
As an effective compound found mainly in the honeybee product propolis, caffeic acid phenethyl ester (CAPE) has been commonly utilized as a medicine and remedial agent, in a number of countries. Specifically, it might inhibit nuclear factor kappa B at micromolar concentrations and demonstrate antioxidant, antineoplastic, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and anti-inflammatory features. This review article summarizes the recent progress regarding the favorable effects of CAPE on a number of eye disease models, including cataract and posterior capsule opacification, corneal diseases, retina and optic nerve-related diseases, ischemia/reperfusion injury of retina, inflammation and infection-related diseases. CAPE has been found to exhibit promising efficacy, with minimal adverse effects, in animal and cell culture studies of several eye diseases.
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Affiliation(s)
- Sumeyya Akyol
- 1 Division of Laboratory Techniques, Vocational School of Medical Sciences, Turgut Ozal University , Ankara, Turkey
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Dey A, Lakshmanan J. The role of antioxidants and other agents in alleviating hyperglycemia mediated oxidative stress and injury in liver. Food Funct 2014; 4:1148-84. [PMID: 23760593 DOI: 10.1039/c3fo30317a] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Several antioxidants and agents having similar antioxidant effects are known to exert beneficial effects in ameliorating the injurious effects of hyperglycemia on liver in different diabetic in vitro and in vivo models. The review deals with some of the agents which have been shown to exert protective effects on liver against hyperglycemic insult and the various mechanisms involved. The different classes of agents which protect the diabetic liver or decrease the severity of hyperglycemia mediated injury include flavonoids, catechins, and other polyphenolic compounds, curcumin and its derivatives, certain vitamins, hormones and drugs, trace elements, prototypical antioxidants and amino acids. Some of the pronounced changes mediated by the antioxidants in liver exposed to hyperglycemia include decreased oxidative stress, and alterations in carbohydrate and lipid metabolism. Other mechanisms through which the agents ameliorate hyperglycemia mediated liver injury include decrease in oxidative DNA and protein damage, restoration of mitochondrial structural and functional integrity, decrease in inflammation and improved insulin signaling. Thus, antioxidants may prove to be an important mode of defense in maintaining normal hepatic functions in diabetes.
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Affiliation(s)
- Aparajita Dey
- Life Science Division, AU-KBC Research Centre, MIT Campus of Anna University, Chromepet, Chennai 600044, India.
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Matough FA, Budin SB, Hamid ZA, Abdul-Rahman M, Al-Wahaibi N, Mohammed J. Tocotrienol-rich fraction from palm oil prevents oxidative damage in diabetic rats. Sultan Qaboos Univ Med J 2014; 14:e95-e103. [PMID: 24516761 DOI: 10.12816/0003342] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Revised: 06/29/2013] [Accepted: 09/22/2013] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES This study was carried out to determine the effects of tocotrienol-rich fraction (TRF) (200 mg/Kg) on biomarkers of oxidative stress on erythrocyte membranes and leukocyte deoxyribonucleic acid (DNA) damage in streptozotocin (STZ)-induced diabetic rats. METHODS Male rats (n = 40) were divided randomly into four groups of 10: a normal group; a normal group with TRF; a diabetic group, and a diabetic group with TRF. Following four weeks of treatment, fasting blood glucose (FBG) levels, oxidative stress markers and the antioxidant status of the erythrocytes were measured. RESULTS FBG levels for the STZ-induced diabetic rats were significantly increased (P <0.001) when compared to the normal group and erythrocyte malondialdehyde levels were also significantly higher (P <0.0001) in this group. Decreased levels of reduced glutathione and increased levels of oxidised glutathione (P <0.001) were observed in STZ-induced diabetic rats when compared to the control group and diabetic group with TRF. The results of the superoxide dismutase and glutathione peroxidase activities were significantly lower in the STZ-induced diabetic rats than in the normal group (P <0.001). The levels of DNA damage, measured by the tail length and tail moment of the leukocyte, were significantly higher in STZ-induced diabetic (P <0.0001). TRF supplementation managed to normalise the level of DNA damage in diabetic rats treated with TRF. CONCLUSION Daily supplementation with 200 mg/Kg of TRF for four weeks was found to reduce levels of oxidative stress markers by inhibiting lipid peroxidation and increasing the levels of antioxidant status in a prevention trial for STZ-induced diabetic rats.
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Affiliation(s)
- Fatmah A Matough
- Department of Biology, Faculty of Science, Sabha University, Sabha, Libya
| | - Siti B Budin
- Programme of Biomedical Sciences, School of Diagnostic Applied Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malayasia
| | - Zariyantey A Hamid
- Programme of Biomedical Sciences, School of Diagnostic Applied Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malayasia
| | - Mariati Abdul-Rahman
- Department of Clinical Oral Biology, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malayasia
| | - Nasar Al-Wahaibi
- Department of Pathology, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Jamaludine Mohammed
- Programme of Biomedical Sciences, School of Diagnostic Applied Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malayasia
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Naik SR, Niture NT, Ansari AA, Shah PD. Anti-diabetic activity of embelin: involvement of cellular inflammatory mediators, oxidative stress and other biomarkers. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2013; 20:797-804. [PMID: 23597490 DOI: 10.1016/j.phymed.2013.03.003] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 02/06/2013] [Accepted: 03/09/2013] [Indexed: 06/02/2023]
Abstract
Embelin (benzoquinone), an active constituent of methanolic extracts of the fruit of Embelia basal (Myrsinaceae), was studied in high fat diet (HFD)+streptozotocin (STZ) diabetic rats. Treatment of embelin (25 and 50 mg/kg/day, p.o.) for 3 weeks to HFD+STZ diabetic rats elicited insignificant increase in body weight, reduced the elevated plasma glucose, glycosylated haemoglobin and pro-inflammatory mediators (interleukin 6 and tumour necrosis factor α) significantly. Furthermore, embelin treatment at both the doses significantly decreased the elevated malondialdehyde, restored depleted glutathione, antioxidant enzymes, superoxide dismutase and catalase in liver. The increased lipid profiles in HFD+STZ diabetic rats were also reduced by embelin treatment significantly. Embelin treatment to HFD+STZ diabetic rats also improved the altered histoarchitecture of β-islets of pancreas and hepatocytes. The embelin effect on progression of type 2 diabetes mellitus in rats appears to be through the inhibition of intracellular pro-inflammatory mediators, lowering of lipid profile and amelioration of oxidative stress. Considering the pharmacological activity profile of embelin, it is suggested that embelin be a useful diabetic modulator or adjuvant along with clinically effective anti-diabetic drugs in the treatment of type 2 diabetes mellitus and needs to be clinically evaluated on human subjects.
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Affiliation(s)
- Suresh R Naik
- Sinhgad Institute of Pharmaceutical Sciences, Kusgaon-Bk, Lonavala, Pune 410401, India.
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Kim SO, Kim HJ. Berberine ameliorates cold and mechanical allodynia in a rat model of diabetic neuropathy. J Med Food 2013; 16:511-7. [PMID: 23734996 DOI: 10.1089/jmf.2012.2648] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
This study evaluated the antiallodynic properties of berberine on cold and mechanical allodynia after streptozotocin (STZ)-induced diabetes using a rat model. Diabetic neuropathy was induced in rats by intraperitoneal injection of STZ. To measure cold and mechanical allodynia, a 4°C plate and von Frey filament were used, respectively. Cold and mechanical allodynia induced by diabetes were significantly decreased by single and repeated intraperitoneal treatment of amitriptyline at 10 mg/kg, and berberine at 10 and 20 mg/kg. The hepatic malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase activities were significantly increased in diabetic rats as compared with those in intact rats; however, in amitriptyline- and berberine-treated rats, they were significantly decreased as compared to the STZ control. The overall effects of berberine 20 mg/kg on cold and mechanical allodynia were quite similar to those of amitriptyline 10 mg/kg, and berberine exhibited similar antioxidant effects as the same dosage of amitriptyline. In conclusion, berberine (10 and 20 mg/kg) was observed to have antiallodynic effects against diabetes, which are presumed to be associated with antioxidative effects. It can be considered that the anti-inflammatory or antidepressant capacity of berberine could contribute to the antiallonynic effects shown in this study.
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Affiliation(s)
- Si Oh Kim
- Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Daegu, Korea
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Saddala RR, Thopireddy L, Ganapathi N, Kesireddy SR. Regulation of cardiac oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with aqueous extract of Pimpinella tirupatiensis tuberous root. ACTA ACUST UNITED AC 2013; 65:15-9. [DOI: 10.1016/j.etp.2011.05.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Revised: 04/17/2011] [Accepted: 05/04/2011] [Indexed: 02/04/2023]
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