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Sun Z, Yu C, Zhang Z, Hu C, Li X, Dong X, Zhang R, Zhang Z, Zhu T, Su X, Guo J. Efficacy of melatonin as adjunctive therapy for sepsis: A meta-analysis of randomized controlled trials. Complement Ther Med 2025; 89:103147. [PMID: 39988019 DOI: 10.1016/j.ctim.2025.103147] [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: 09/04/2024] [Revised: 02/04/2025] [Accepted: 02/18/2025] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND This study systematically evaluates the therapeutic efficacy of melatonin as an adjunctive therapy, aiming to determine its potential to reduce mortality and mitigate inflammatory responses in patients with sepsis. METHODS A search was conducted across PubMed, Web of Science, Cochrane Library, and Embase databases. The Cochrane Collaboration Risk of Bias (ROB) tool was systematically employed to assess the potential for bias in the relevant studies. The I² statistic was employed to evaluate heterogeneity among the studies. Potential publication bias was assessed using Begg's test. Sensitivity analysis was performed to examine the stability of the results. Additionally, a GRADE evaluation of the evidence level. RESULTS This meta-analysis encompassed a total of seven randomized controlled trials involving 421 patients diagnosed with sepsis. The primary results indicated that the mortality rate in the intervention group was significantly lower than that in the control group, suggesting that melatonin may effectively reduce mortality among sepsis patients [OR = 0.42, 95 % CI: 0.23-0.77, P = 0.005]. Additionally, the CRP levels in the intervention group were markedly lower than those in the control group, providing evidence that melatonin possesses anti-inflammatory properties that may help decrease inflammatory markers in sepsis patients [SMD= -4.00, 95 % CI: -6.47 to -1.53, P = 0.001]. Furthermore, Secondary outcome results showed no statistically significant differences in sequential organ failure assessment (SOFA) scores, length of hospital stay, and adverse effects. A sensitivity analysis confirmed the robustness of the findings from the included studies. By applying the GRADE system to evaluate the quality of evidence, we found the evidence in four grades: one rated as high quality, one as medium quality, and three rated as low quality. CONCLUSION Melatonin, when used as an adjuvant therapy, significantly reduces mortality and lowers the levels of the inflammatory marker CRP in patients with sepsis, while also improving their physical condition. However, due to the limited number and quality of the articles, these conclusions warrant further verification through the conduct of additional high-quality research.
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Affiliation(s)
- Zhuangzhuang Sun
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Cheng Yu
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Zhaopeng Zhang
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Chunjie Hu
- The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Xin Li
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Xiheng Dong
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Ru Zhang
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Zhirun Zhang
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Tonggang Zhu
- The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun 130021, China
| | - Xin Su
- Changchun University of Chinese Medicine, Changchun 130117, China
| | - Junpeng Guo
- Changchun University of Chinese Medicine, Changchun 130117, China.
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Laurindo LF, Simili OAG, Araújo AC, Guiguer EL, Direito R, Valenti VE, de Oliveira V, de Oliveira JS, Yanaguizawa Junior JL, Dias JA, Maria DA, Rici REG, Bueno MDS, Sloan KP, Sloan LA, Barbalho SM. Melatonin from Plants: Going Beyond Traditional Central Nervous System Targeting-A Comprehensive Review of Its Unusual Health Benefits. BIOLOGY 2025; 14:143. [PMID: 40001911 PMCID: PMC11851571 DOI: 10.3390/biology14020143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Revised: 01/24/2025] [Accepted: 01/26/2025] [Indexed: 02/27/2025]
Abstract
Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time.
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Affiliation(s)
- Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Otávio Augusto Garcia Simili
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Adriano Cressoni Araújo
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Elen Landgraf Guiguer
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Marília 17500-000, SP, Brazil
| | - Rosa Direito
- Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines, Universidade de Lisboa (iMed.ULisboa), Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Vitor Engrácia Valenti
- Autonomic Nervous System Center, School of Philosophy and Sciences, São Paulo State University, Marília 17525-902, SP, Brazil
| | - Vitor de Oliveira
- Department of Biochemistry and Pharmacology, School of Medicine, New York Medical College, New York, NY 10595, USA
| | - Juliana Santos de Oliveira
- Department of Biochemistry and Pharmacology, School of Medicine, University of Miami, Coral Gables, FL 33146, USA
| | - José Luiz Yanaguizawa Junior
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Jefferson Aparecido Dias
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | - Durvanei Augusto Maria
- Development and Innovation Laboratory, Butantan Institute, São Paulo 05585-000, SP, Brazil
| | - Rose Eli Grassi Rici
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Graduate Program in Anatomy of Domestic and Wild Animals, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-220, SP, Brazil
| | - Manuela dos Santos Bueno
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
| | | | - Lance Alan Sloan
- Texas Institute for Kidney and Endocrine Disorders, Lufkin, TX 75904, USA
- Clinical Department, School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Marília 17500-000, SP, Brazil
- UNIMAR Charity Hospital, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil
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de Man AME, Amrein K, Casaer MP, Dizdar OS, van Zanten ARH, Gundogan K, Lepp L, Rezzi S, Shenkin A, Berger MM. LLL 44-4 : Micronutrients in acute disease and critical illness. Clin Nutr ESPEN 2024; 61:437-446. [PMID: 38777466 DOI: 10.1016/j.clnesp.2024.04.011] [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: 03/17/2024] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 05/25/2024]
Abstract
Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed.
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Affiliation(s)
- Angélique M E de Man
- Amsterdam UMC, Location Vrije Universiteit, Department of Intensive Care, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Oguzhan S Dizdar
- Department of Internal Medicine and Clinical Nutrition Unit, University of Health Sciences Kayseri City Training and Research Hospital, Kayseri, Turkey.
| | - Arthur R H van Zanten
- Gelderse Vallei Hospital, Ede and Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey; North Estonia Regional Hospital, Tallinn, Estonia.
| | - Liis Lepp
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation, Epalinges, Switzerland.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Mette M Berger
- Faculty of Biology & Medicine, Lausanne University, Lausanne, Switzerland.
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Casper E, El Wakeel L, Sabri N, Khorshid R, Fahmy SF. Melatonin: A potential protective multifaceted force for sepsis-induced cardiomyopathy. Life Sci 2024; 346:122611. [PMID: 38580195 DOI: 10.1016/j.lfs.2024.122611] [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: 11/16/2023] [Revised: 03/19/2024] [Accepted: 04/02/2024] [Indexed: 04/07/2024]
Abstract
Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are among the affected organs. Sepsis-induced cardiomyopathy is a common cause of death among septic patients. Sepsis-induced cardiomyopathy is characterized by an acute and reversible significant decline in biventricular both systolic and diastolic function. This is accompanied by left ventricular dilatation. The pathogenesis underlying sepsis-induced cardiomyopathy is multifactorial. Hence, targeting an individual pathway may not be effective in halting the extensive dysregulated immune response. Despite major advances in sepsis management strategies, no effective pharmacological strategies have been shown to treat or even reverse sepsis-induced cardiomyopathy. Melatonin, namely, N-acetyl-5-methoxytryptamine, is synthesized in the pineal gland of mammals and can also be produced in many cells and tissues. Melatonin has cardioprotective, neuroprotective, and anti-tumor activity. Several literature reviews have explored the role of melatonin in preventing sepsis-induced organ failure. Melatonin was found to act on different pathways that are involved in the pathogenesis of sepsis-induced cardiomyopathy. Through its antimicrobial, anti-inflammatory, and antioxidant activity, it offers a potential role in sepsis-induced cardiomyopathy. Its antioxidant activity is through free radical scavenging against reactive oxygen and nitrogen species and modulating the expression and activity of antioxidant enzymes. Melatonin anti-inflammatory activities control the overactive immune system and mitigate cytokine storm. Also, it mitigates mitochondrial dysfunction, a major mechanism involved in sepsis-induced cardiomyopathy, and thus controls apoptosis. Therefore, this review discusses melatonin as a promising drug for the management of sepsis-induced cardiomyopathy.
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Affiliation(s)
- Eman Casper
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - Lamia El Wakeel
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - Nagwa Sabri
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - Ramy Khorshid
- Department of Cardiovascular and Thoracic Surgery, Ain Shams University Hospital, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Sarah F Fahmy
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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Pham TPT, Le THT, Pham HTX, Tran TT, Pham VT, Mafruhah OR, Ha HA. Comparative efficacy of antioxidant therapies for sepsis and septic shock in the intensive care unit: A frequentist network meta-analysis. Heliyon 2024; 10:e31447. [PMID: 38807867 PMCID: PMC11130736 DOI: 10.1016/j.heliyon.2024.e31447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/15/2024] [Accepted: 05/15/2024] [Indexed: 05/30/2024] Open
Abstract
Background Antioxidant therapy is gaining traction in managing sepsis and septic shock, owing to its perceived positive impact on patient outcomes. This study sought to compare the efficacy of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium, and N-acetylcysteine, both individually and in combination with other compounds such as vitamin B1, hydrocortisone, propolis, and glutamine) in treating sepsis or septic shock in the intensive care unit (ICU). Methods The study involved randomized and multi-arm trials with sepsis or septic shock patients using melatonin, vitamin C, vitamin E, selenium, or N-acetylcysteine. Studies were sourced from PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO - Clinical Trials Registry Platform for the frequentist network meta-analysis on 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores. The risk of bias was assessed using the Physiotherapy Evidence Database scale. Therapies were compared directly and indirectly using R software. Results The study of 56 trials involving 9,366 patients was included. Bias assessment revealed that 89.3 % of trials achieved excellent or good quality. Based on treatment ranking and pairwise comparisons, melatonin with propolis (SUCRA = 93.29 %) is effective in improving SOFA scores, statistically significant, with no publication bias (p= 0.73). High-dose vitamin C (SUCRA = 83.97 %), vitamin C with vitamin B1 (SUCRA = 78.72 %), and melatonin (SUCRA = 67.03 %) are potential therapies for organ dysfunction. Melatonin (SUCRA = 88.22 %) and high-dose vitamin C (SUCRA = 80.75 %) were the most effective in reducing 28-day mortality rates. However, analysis indicated that the results for 28-day mortality rates were not statistically significant. Also, these results contained publication bias (p= 0.02). Conclusion The study offers fresh perspectives on antioxidant therapy treatments for sepsis or septic shock in ICU, emphasizing the combination of melatonin and propolis notably reduces SOFA scores for those patients.
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Affiliation(s)
- Thi-Phuong-Thao Pham
- Research and Development Department, HerbiTech Co. Ltd, Ha Noi, 100000, Viet Nam
| | - Thi-Hoai-Thu Le
- K25YDH3, College of Medicine and Pharmacy, Duy Tan University, Danang 550000, Viet Nam
| | - Huynh-Thien-Xuan Pham
- K26YDH2, College of Medicine and Pharmacy, Duy Tan University, Danang 550000, Viet Nam
| | - Thanh-Thien Tran
- K27YDH1, College of Medicine and Pharmacy, Duy Tan University, Danang 550000, Viet Nam
| | - Van-Truong Pham
- Intensive Care Unit - Hospital 199 - Ministry of Public Security, Danang 550000, Viet Nam
| | - Okti Ratna Mafruhah
- Department of Pharmacy, Universitas Islam Indonesia, Daerah Istimewa Yogyakarta, 55584, Indonesia
| | - Hai-Anh Ha
- Faculty of Pharmacy, College of Medicine and Pharmacy, Duy Tan University, Danang 550000, Viet Nam
- Da Nang Pharmaceutical Association, Da Nang, 550000, Viet Nam
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Yong S, Suping L, Peng Z, Dong L, Qing W. The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2024; 103:e37420. [PMID: 38518058 PMCID: PMC10956978 DOI: 10.1097/md.0000000000037420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 02/07/2024] [Indexed: 03/24/2024] Open
Abstract
BACKGROUND Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. METHODS Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). RESULTS There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). CONCLUSION This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.
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Affiliation(s)
- Su Yong
- Intensive Care Unit, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Liu Suping
- Intensive Care Unit, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Zhang Peng
- Department of Gastrointestinal Surgery, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Lin Dong
- Department of Urology, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Wei Qing
- Intensive Care Unit, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
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Sahoo DK, Wong D, Patani A, Paital B, Yadav VK, Patel A, Jergens AE. Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review. Front Cell Infect Microbiol 2024; 14:1348713. [PMID: 38510969 PMCID: PMC10952105 DOI: 10.3389/fcimb.2024.1348713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 02/15/2024] [Indexed: 03/22/2024] Open
Abstract
Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.
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Affiliation(s)
- Dipak Kumar Sahoo
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - David Wong
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Anil Patani
- Department of Biotechnology, Smt. S. S. Patel Nootan Science and Commerce College, Sankalchand Patel University, Gujarat, India
| | - Biswaranjan Paital
- Redox Regulation Laboratory, Department of Zoology, College of Basic Science and Humanities, Odisha University of Agriculture and Technology, Bhubaneswar, India
| | - Virendra Kumar Yadav
- Department of Life Sciences, Hemchandracharya North Gujarat University, Gujarat, India
| | - Ashish Patel
- Department of Life Sciences, Hemchandracharya North Gujarat University, Gujarat, India
| | - Albert E. Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
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Üstündağ H, Demir Ö, Huyut MT, Yüce N. Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats. Sci Rep 2024; 14:3098. [PMID: 38326366 PMCID: PMC10850075 DOI: 10.1038/s41598-024-52932-5] [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: 09/01/2023] [Accepted: 01/25/2024] [Indexed: 02/09/2024] Open
Abstract
Sepsis-induced cardiac injury represents a major clinical challenge, amplifying the urgency for effective therapeutic interventions. This study aimed to delve into the individual and combined prophylactic effects of Vitamin C (Vit C) and Coenzyme Q10 (CoQ10) against inflammatory heart injury in a cecal ligation and puncture (CLP) induced polymicrobial sepsis rat model. Thirty adult female Sprague-Dawley rats were randomly divided into five groups: Control, CLP, Vitamin C, CoQ10, and Vit C + CoQ10, each consisting of six rats. Treatments were administered orally via gavage for 10 days prior to the operation. Eighteen hours post-sepsis induction, the animals were euthanized, and specimens were collected for analysis. The study examined variations in oxidative (TOS, OSI, MDA, MPO) and antioxidative markers (TAS, SOD, CAT, GSH), histopathological changes, inflammatory cytokine concentrations (TNF-α, IL-1β), nitric oxide (NO) dynamics, and cardiac indicators such as CK-MB. Impressively, the combined regimen markedly diminished oxidative stress, and antioxidative parameters reflected notable enhancements. Elevated NO levels, a central player in sepsis-driven inflammatory cascades, were effectively tempered by our intervention. Histological examinations corroborated the biochemical data, revealing diminished cardiac tissue damage in treated subjects. Furthermore, a marked suppression in pro-inflammatory cytokines was discerned, solidifying the therapeutic potential of our intervention. Interestingly, in certain evaluations, CoQ10 exhibited superior benefits over Vit C. Collectively, these findings underscore the potential therapeutic promise of Vit C and CoQ10 combination against septic cardiac injuries in rats.
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Affiliation(s)
- Hilal Üstündağ
- Department of Physiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Türkiye.
| | - Özlem Demir
- Department of Histology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Türkiye
| | - Mehmet Tahir Huyut
- Department of Biostatistics, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Türkiye
| | - Neslihan Yüce
- Department of Biochemistry, Faculty of Medicine, Atatürk University, Erzurum, Türkiye
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Dicle Y, Aydin E, Seker U. Investigation of the protective activity of baicalein on the lungs via regulation of various cellular responses in rats exposed to experimental sepsis. Toxicol Res (Camb) 2024; 13:tfad112. [PMID: 38178997 PMCID: PMC10762668 DOI: 10.1093/toxres/tfad112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 10/27/2023] [Accepted: 11/20/2023] [Indexed: 01/06/2024] Open
Abstract
Backgrounds In the present study, a cecal ligation and puncture (CLP)-induced experimental sepsis rat model was used to explore the effects of baicalein on inflammatory cytokine levels and oxidative stress as well as the possible regulatory role of nuclear factor-kappa B (NF-κB). Methods For that purpose, 42 Wistar albino rats were equally divided into control, sham, sepsis, B50 + S, B100 + S, S + B50, and S + B100 groups. The B50 + S and B100 + S groups received baicalein before the induction of sepsis, while the S + B50 and S + B100 groups received baicalein afterwards. Experimental sepsis in related groups is generated through ligation of cecum and a puncture in cecal wall. Serum samples were used for tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) analyses, and tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), IL-6, and NF-κB levels were measured. Results Compared to the control group, there were significantly increases in the serum TNF-α, IL-6, tissue MDA, and NF-κB levels and decreases in the tissue SOD and GSH levels in the septic group (P < 0.05). Compared to the septic group, inflammation and oxidative stress were reduced in the baicalein-treated groups. Although all of the pre- and post-treatment protocols alleviated inflammation and oxidative stress to varying degrees, pre-treatment with 100 mg/kg was the most successful. Conclusions Findings of this study indicated that baicalein has the potential to reduce sepsis-related oxidative stress and inflammation in the lungs and that pathological outcomes could be regulated via NF-κB transcription factor activity.
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Affiliation(s)
- Yalcin Dicle
- Department of Medical Microbiology, Faculty of Medicine, Mardin Artuklu University, 47200, Mardin, Türkiye
| | - Elif Aydin
- Tavsanli Vocational School of Health Services, Kutahya Health Sciences University, 43300, Kutahya, Türkiye
| | - Ugur Seker
- Department of Histology and Embryology, Faculty of Medicine, Mardin Artuklu University, 47200, Mardin, Türkiye
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Pérez-Torres I, Aisa-Álvarez A, Casarez-Alvarado S, Borrayo G, Márquez-Velasco R, Guarner-Lans V, Manzano-Pech L, Cruz-Soto R, Gonzalez-Marcos O, Fuentevilla-Álvarez G, Gamboa R, Saucedo-Orozco H, Franco-Granillo J, Soto ME. Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects. Int J Mol Sci 2023; 24:16610. [PMID: 38068931 PMCID: PMC10706209 DOI: 10.3390/ijms242316610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/14/2023] [Accepted: 11/18/2023] [Indexed: 12/18/2023] Open
Abstract
Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1β, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFβ), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.
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Affiliation(s)
- Israel Pérez-Torres
- Cardiovascular Biomedicine Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (I.P.-T.); (L.M.-P.)
| | - Alfredo Aisa-Álvarez
- Critical Care Department, American British Cowdray (ABC) Medical Center, PAI ABC Sur 136 No. 116, Col. las Américas, Mexico City 01120, Mexico; (A.A.-Á.); (O.G.-M.); (J.F.-G.)
| | - Sergio Casarez-Alvarado
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (S.C.-A.); (R.M.-V.); (R.C.-S.)
| | - Gabriela Borrayo
- Instituto Mexicano del Seguro Social, Dirección de Prestaciones Médicas Coordinación de Innovación en Salud, Ciudad de México 06700, Mexico;
| | - Ricardo Márquez-Velasco
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (S.C.-A.); (R.M.-V.); (R.C.-S.)
| | - Verónica Guarner-Lans
- Physiology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (V.G.-L.); (G.F.-Á.); (R.G.)
| | - Linaloe Manzano-Pech
- Cardiovascular Biomedicine Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (I.P.-T.); (L.M.-P.)
| | - Randall Cruz-Soto
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (S.C.-A.); (R.M.-V.); (R.C.-S.)
| | - Omar Gonzalez-Marcos
- Critical Care Department, American British Cowdray (ABC) Medical Center, PAI ABC Sur 136 No. 116, Col. las Américas, Mexico City 01120, Mexico; (A.A.-Á.); (O.G.-M.); (J.F.-G.)
| | - Giovanny Fuentevilla-Álvarez
- Physiology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (V.G.-L.); (G.F.-Á.); (R.G.)
| | - Ricardo Gamboa
- Physiology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (V.G.-L.); (G.F.-Á.); (R.G.)
| | | | - Juvenal Franco-Granillo
- Critical Care Department, American British Cowdray (ABC) Medical Center, PAI ABC Sur 136 No. 116, Col. las Américas, Mexico City 01120, Mexico; (A.A.-Á.); (O.G.-M.); (J.F.-G.)
| | - María Elena Soto
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico; (S.C.-A.); (R.M.-V.); (R.C.-S.)
- Research Direction Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Mexico City 14380, Mexico
- Cardiovascular Line in American British Cowdray (ABC) Medical Center, PAI ABC Sur 136 No. 116, Col. Las Américas, Mexico City 01120, Mexico
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Sieminski M, Szaruta-Raflesz K, Szypenbejl J, Krzyzaniak K. Potential Neuroprotective Role of Melatonin in Sepsis-Associated Encephalopathy Due to Its Scavenging and Anti-Oxidative Properties. Antioxidants (Basel) 2023; 12:1786. [PMID: 37760089 PMCID: PMC10525116 DOI: 10.3390/antiox12091786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/08/2023] [Accepted: 09/20/2023] [Indexed: 09/29/2023] Open
Abstract
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The brain is one of the organs involved in sepsis, and sepsis-induced brain injury manifests as sepsis-associated encephalopathy (SAE). SAE may be present in up to 70% of septic patients. SAE has a very wide spectrum of clinical symptoms, ranging from mild behavioral changes through cognitive disorders to disorders of consciousness and coma. The presence of SAE increases mortality in the population of septic patients and may lead to chronic cognitive dysfunction in sepsis survivors. Therefore, therapeutic interventions with neuroprotective effects in sepsis are needed. Melatonin, a neurohormone responsible for the control of circadian rhythms, exerts many beneficial physiological effects. Its anti-inflammatory and antioxidant properties are well described. It is considered a potential therapeutic factor in sepsis, with positive results from studies on animal models and with encouraging results from the first human clinical trials. With its antioxidant and anti-inflammatory potential, it may also exert a neuroprotective effect in sepsis-associated encephalopathy. The review presents data on melatonin as a potential drug in SAE in the wider context of the pathophysiology of SAE and the specific actions of the pineal neurohormone.
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Affiliation(s)
- Mariusz Sieminski
- Department of Emergency Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (K.S.-R.); (K.K.)
| | | | - Jacek Szypenbejl
- Department of Emergency Medicine, Medical University of Gdansk, 80-214 Gdansk, Poland; (K.S.-R.); (K.K.)
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Kılıç GA, Alsafi M. β-Glucan Regulates Lipopolysaccharide Induced Genotoxic Damage to The Liver through The Induction of BRCA1 Protein Expression. CELL JOURNAL 2023; 25:645-654. [PMID: 37718767 PMCID: PMC10520986 DOI: 10.22074/cellj.2023.1989382.1226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/20/2023] [Accepted: 05/14/2023] [Indexed: 09/19/2023]
Abstract
OBJECTIVE The present study aims to investigate the role of breast cancer-susceptibility gene 1 (BRCA1) protein in the β-Glucan (βG) molecule mediated regulation of lipopolysaccharide (LPS)-induced liver genotoxicity. MATERIALS AND METHODS In this experimental study, totally, 32 male Swiss Albino mice were randomly divided into 4 equal groups: control (C), LPS-administered (LPS), βG-administered (βG) and βG-pre-administered/LPS-administered (βG+LPS). The βG was injected at the dose of 150 mg/kg/day intraperitoneally (i.p.) for 3 days. A single dose of 4 mg/ kg (i.p.) LPS was administered 24 hours after the last βG injection. BRCA1 expression was determined by western blot analysis and confirmed by quantitative immunofluorescence. Proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor (Nrf2) and 8-OHdG protein levels were also determined by the immunofluorescence analysis. The alkaline comet assay was performed. superoxide dismutase (SOD), catalase (CAT) and membrane lipid peroxidation were biochemically measured, and light microscopic histology was evaluated. RESULTS The BRCA1 expression level was significantly decreased in the LPS group. However, in the βG+LPS group, expression of BRCA1 protein was over 2 folds higher than the control. After the LPS induction, the DNA strand breaks, oxidative DNA lesions and abnormal proliferation of the liver cells were almost entirely suppressed in βG preadministrated animals, indicating the BRCA1 mediated ubiquitination of PCNA and activation of the DNA damage repair pathways. Activation of Nrf2 in the βG+LPS group resulted in an increase in the levels of Nrf2 pathway dependent antioxidant enzymes SOD and CAT, prevented the peroxidation of membrane lipids and maintained the histological architecture of the liver. CONCLUSION The results manifested that the βG is a strong inducer of the BRCA1 protein expression in the LPSinduced hepatic stress and the protein constitutes the key component of a βG mediated liver protection against an LPS-induced genotoxic and pathological damage.
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Affiliation(s)
- Gözde Aydoğan Kılıç
- Department of Biology, Faculty of Science, Eskişehir Technical University, Eskişehir, Turkey
| | - Mojahed Alsafi
- Department of Biology, Faculty of Science, Eskişehir Technical University, Eskişehir, Turkey
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Alvi MM, Imtiaz N, Shabbir B, Waheed Z, Atta-ur-Rehman. Evaluating the role of antioxidant therapy in outcome of severe and critical COVID-19 infection requiring high flow oxygen. Lung India 2023; 40:333-338. [PMID: 37417086 PMCID: PMC10401983 DOI: 10.4103/lungindia.lungindia_369_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 11/01/2022] [Accepted: 11/08/2022] [Indexed: 07/08/2023] Open
Abstract
Objective To determine the efficacy of antioxidant therapy in the outcome of critical COVID-19-infected patients. Methods At the Patel Hospital, a retrospective cohort analysis was carried out between June 2020 and October 2021. The study included a record of 200 individuals with severe or critical stage COVID-19 who were older than 18 and of either gender. Based on the antioxidant therapy, study participants were placed evenly into two groups. Antioxidant therapy was provided to one group (the exposed group), whereas the other group received simply normal COVID-19 medication (the unexposed group). Outcomes from both groups were evaluated and compared. Results Patients on antioxidant therapy had lesser mortality and shorter hospital stay than patients on coventional management, but the difference in proportions of mortality and length of hospital stay was statistically insignificant between groups (p > 0.05). Patients on antioxidant therapy had a significantly higher proportion of moderate to severe ARDS and septic shock than unexposed patients. A significantly higher number of patients in the unexposed group had AKI as compared to the exposed group (p = 0.048). Conclusions Antioxidant therapy seems to have a non-significant positive effect on mortality, hospital stay, and AKI, while it showed a negative effect on the severity of ARDS and septic shock.
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Affiliation(s)
- Malick Maria Alvi
- Department of Medicine, Patel Hospital, Street 18, Block 4, Gulshan-e-Iqbal, Karachi, Pakistan
| | - Nimra Imtiaz
- Department of Medicine, Patel Hospital, Street 18, Block 4, Gulshan-e-Iqbal, Karachi, Pakistan
| | - Bushra Shabbir
- Department of Medicine, Patel Hospital, Street 18, Block 4, Gulshan-e-Iqbal, Karachi, Pakistan
| | - Zeeshan Waheed
- Department of Medicine, Patel Hospital, Street 18, Block 4, Gulshan-e-Iqbal, Karachi, Pakistan
| | - Atta-ur-Rehman
- Department of Medicine, Patel Hospital, Street 18, Block 4, Gulshan-e-Iqbal, Karachi, Pakistan
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Aisa-Álvarez A, Pérez-Torres I, Guarner-Lans V, Manzano-Pech L, Cruz-Soto R, Márquez-Velasco R, Casarez-Alvarado S, Franco-Granillo J, Núñez-Martínez ME, Soto ME. Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System. Cells 2023; 12:cells12091330. [PMID: 37174730 PMCID: PMC10177152 DOI: 10.3390/cells12091330] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 04/28/2023] [Accepted: 04/30/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND AND AIM Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.
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Affiliation(s)
- Alfredo Aisa-Álvarez
- Critical Care Department, American British Cowdray (ABC) Medical Center, I.A.P. ABC Sur 136 No. 116 Col. Las Américas, México City 01120, Mexico
- UNAM Master's and Doctoral Program in Medical, Dental and Health Sciences UNAM, México. Av. Universidad 3000, Coyoacán, México City 04510, Mexico
| | - Israel Pérez-Torres
- Cardiovascular Biomedicine Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Verónica Guarner-Lans
- Physiology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Linaloe Manzano-Pech
- Cardiovascular Biomedicine Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Randall Cruz-Soto
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Ricardo Márquez-Velasco
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Sergio Casarez-Alvarado
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Juvenal Franco-Granillo
- Critical Care Department, American British Cowdray (ABC) Medical Center, I.A.P. ABC Sur 136 No. 116 Col. Las Américas, México City 01120, Mexico
| | | | - María Elena Soto
- Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
- Department of the Cardiovascular, Division of the American British Cowdray Medical Center, Sur 136 No. 116 Col. Las Américas, México City 01120, Mexico
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Soto ME, Manzano-Pech L, Palacios-Chavarría A, Valdez-Vázquez RR, Guarner-Lans V, Pérez-Torres I. N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings. Pharmaceuticals (Basel) 2023; 16:ph16040591. [PMID: 37111348 PMCID: PMC10146435 DOI: 10.3390/ph16040591] [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: 03/06/2023] [Revised: 04/11/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023] Open
Abstract
SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the study is to evaluate the effect of the treatment with NAC on the enzymatic antioxidant system in serum from patients infected by SARS-CoV-2. We evaluated the enzymatic activities of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), -S-transferase (GST), and reductase (GR) by spectrophotometry and the concentrations of the glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), and lipid peroxidation (LPO) in serum. The activity of the extracellular super oxide dismutase (ecSOD) was determined by native polyacrylamide gels, and 3-nitrotyrosine (3-NT) was measured by ELISA. A decrease in the activities of the ecSOD, TrxR, GPx, GST GR, (p = 0 ≤ 0.1), and the GSH, TAC, thiols, and NO2- (p ≤ 0.001) concentrations and an increase in LPO and 3-NT (p = 0.001) concentrations were found in COVID-19 patients vs. healthy subjects. The treatment with NAC as an adjuvant therapy may contribute to a reduction in the OS associated to the infection by SARS-CoV-2 through the generation of GSH. GSH promotes the metabolic pathways that depend on it, thus contributing to an increase in TAC and to restore redox homeostasis.
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Affiliation(s)
- María Elena Soto
- Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico
| | - Linaloe Manzano-Pech
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | | | | | - Verónica Guarner-Lans
- Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico
| | - Israel Pérez-Torres
- Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico
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Xu C, Yi T, Tan S, Xu H, Hu Y, Ma J, Xu J. Association of Oral or Intravenous Vitamin C Supplementation with Mortality: A Systematic Review and Meta-Analysis. Nutrients 2023; 15:1848. [PMID: 37111066 PMCID: PMC10146309 DOI: 10.3390/nu15081848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/21/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.
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Affiliation(s)
- Chongxi Xu
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Tong Yi
- Department of Neurology, The Second People’s Hospital of Deyang City, No. 340 Minjiang West Road, Deyang 618000, China
| | - Siwen Tan
- Outpatient Department, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Hui Xu
- Department of Neurosurgery, The Second People’s Hospital of Liangshan Yi, Autonomous Prefecture, Liangshan 615000, China
| | - Yu Hu
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Junpeng Ma
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Jianguo Xu
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
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Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial. Inflammopharmacology 2023; 31:265-274. [PMID: 36401728 PMCID: PMC9676876 DOI: 10.1007/s10787-022-01096-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 10/28/2022] [Indexed: 11/21/2022]
Abstract
Patients with COVID-19 have shown melatonin deficiency. We evaluated the efficacy and safety of administration oral melatonin in patients with COVID-19-induced pneumonia. Patients were randomly assigned in a 1:1 ratio to receive melatonin plus standard treatment or standard treatment alone. The primary outcomes were mortality rate and requirement of IMV. The clinical status of patients was recorded at baseline and every day over hospitalization based on seven-category ordinal scale from 1 (discharged) to 7 (death). A total of 226 patients (109 in the melatonin group and 117 in the control group) were enrolled (median age; in melatonin group: 54.60 ± 11.51, in control group: 54.69 ± 13.40). The mortality rate was 67% in the melatonin group and 94% in the control group (OR; 7.75, 95% CI, 3.27-18.35, P < 0.001). The rate of IMV requirement was 51.4% in the melatonin group and 70.9% in the control group, for an OR of 2.31 (95% CI, 1.34-4.00, P < 0.001). The median number of days to hospital discharge was 15 days (13-17) in the melatonin group and 21 days (14-24) in the control group (OR; 5.00, 95% CI, 0.15-9.84, P = 0.026). Time to clinical status improvement by ≥ 2 on the ordinal scale in was 12 days (9-13) in the melatonin group and 16 days (10-19) in the control group (OR; 3.92, 95% CI, 1.69-6.14, P = 0.038). Melatonin significantly improved clinical status with a safe profile in patients with severe COVID-19 pneumonia.
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Potential Antioxidant Multitherapy against Complications Occurring in Sepsis. Biomedicines 2022; 10:biomedicines10123088. [PMID: 36551843 PMCID: PMC9775396 DOI: 10.3390/biomedicines10123088] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/05/2022] [Accepted: 11/10/2022] [Indexed: 12/03/2022] Open
Abstract
Septic shock currently represents one of the main causes of mortality in critical patient units with an increase in its incidence in recent years, and it is also associated with a high burden of morbidity in surviving patients. Within the pathogenesis of sepsis, oxidative stress plays an important role. The excessive formation of reactive oxygen species (ROS) leads to mitochondrial damage and vasomotor dysfunction that characterizes those patients who fall into septic shock. Currently, despite numerous studies carried out in patients with septic shock of different causes, effective therapies have not yet been developed to reduce the morbidity and mortality associated with this pathology. Despite the contribution of ROS in the pathophysiology of sepsis and septic shock, most studies performed in humans, with antioxidant monotherapies, have not resulted in promising data. Nevertheless, some interventions with compounds such as ascorbate, N-acetylcysteine, and selenium would have a positive effect in reducing the morbidity and mortality associated with this pathology. However, more studies are required to demonstrate the efficacy of these therapies. Taking into account the multifactorial features of the pathophysiology of sepsis, we put forward the hypothesis that a supplementation based on the association of more than one antioxidant compound should result in a synergistic or additive effect, thus improving the beneficial effects of each of them alone, potentially serving as a pharmacological adjunct resource to standard therapy to reduce sepsis complications. Therefore, in this review, it is proposed that the use of combined antioxidant therapies could lead to a better clinical outcome of patients with sepsis or septic shock, given the relevance of oxidative stress in the pathogenesis of this multi-organ dysfunction.
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Juneja D, Nasa P, Jain R. Current role of high dose vitamin C in sepsis management: A concise review. World J Crit Care Med 2022; 11:349-363. [PMID: 36439321 PMCID: PMC9693906 DOI: 10.5492/wjccm.v11.i6.349] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/08/2022] [Accepted: 09/09/2022] [Indexed: 02/05/2023] Open
Abstract
Sepsis and septic shock are common diagnoses for patients requiring intensive care unit admission and associated with high morbidity and mortality. In addition to aggressive fluid resuscitation and antibiotic therapy, several other drugs have been tried as adjuvant therapies to reduce the inflammatory response and improve outcomes. Vitamin C has been shown to have several biological actions, including anti-inflammatory and immunomodulatory effects, which may prove beneficial in sepsis management. Initial trials showed improved patient outcomes when high dose vitamin C was used in combination with thiamine and hydrocortisone. These results, along with relative safety of high-dose (supra-physiological) vitamin C, encouraged physicians across the globe to add vitamin C as an adjuvant therapy in the management of sepsis. However, subsequent large-scale randomised control trials could not replicate these results, leaving the world divided regarding the role of vitamin C in sepsis management. Here, we discuss the rationale, safety profile, and the current clinical evidence for the use of high-dose vitamin C in the management of sepsis and septic shock.
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Affiliation(s)
- Deven Juneja
- Institute of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
| | - Prashant Nasa
- Department of Critical Care Medicine, NMC Specialty Hospital, Dubai 7832, United Arab Emirates
| | - Ravi Jain
- Department of Critical Care Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur 302022, Rajasthan, India
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20
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Galley HF, Allen L, Colin PJ, Galt SP, Webster NR. Dose assessment of melatonin in sepsis (DAMSEL2) study: Pharmacokinetics of two doses of oral melatonin in patients with sepsis. J Pineal Res 2022; 73:e12830. [PMID: 36046952 PMCID: PMC9787748 DOI: 10.1111/jpi.12830] [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: 01/07/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 12/30/2022]
Abstract
Sepsis is defined as a dysregulated host response to infection, and high-dose melatonin has been proposed as a treatment due to its antioxidant and anti-inflammatory properties. However, there are no data describing the pharmacokinetics of high-dose oral melatonin in critically ill patients. We undertook an open-label trial to determine the tolerance of melatonin administration in these patients and pharmacokinetic analysis, to inform a planned randomised controlled trial. Two cohorts of critically ill patients with sepsis due to community-acquired pneumonia received either 20 or 50 mg oral melatonin liquid as a single dose. Blood samples and clinical measures were analysed over the next 24 h. Melatonin was well tolerated and there were no adverse events. Pharmacokinetic modelling showed that a semiphysiological model, which incorporates saturable first-pass hepatic extraction, was a good fit for our data. Maximum levels of melatonin were extremely high in patients receiving the 50 mg dose and levels of the major metabolite were much lower than expected and not different from those seen after 20 mg, suggesting saturation at the higher dose. We conclude that 20 mg seems a suitable dose of liquid melatonin in patients with sepsis.
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Affiliation(s)
- Helen F. Galley
- Institute of Medical Sciences, School of Medicine, Medical Sciences and NutritionUniversity of AberdeenAberdeenUK
- Intensive Care Unit, Aberdeen Royal InfirmaryNHS GrampianAberdeenUK
| | - Lee Allen
- Intensive Care Unit, Aberdeen Royal InfirmaryNHS GrampianAberdeenUK
| | - Pieter J. Colin
- Department of Anesthesiology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Sally P. Galt
- Intensive Care Unit, Aberdeen Royal InfirmaryNHS GrampianAberdeenUK
| | - Nigel R. Webster
- Institute of Medical Sciences, School of Medicine, Medical Sciences and NutritionUniversity of AberdeenAberdeenUK
- Intensive Care Unit, Aberdeen Royal InfirmaryNHS GrampianAberdeenUK
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21
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Deodorized Garlic Decreases Oxidative Stress Caused by Lipopolysaccharide in Rat Heart through Hydrogen Sulfide: Preliminary Findings. Int J Mol Sci 2022; 23:ijms232012529. [PMID: 36293383 PMCID: PMC9604113 DOI: 10.3390/ijms232012529] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/08/2022] [Accepted: 10/15/2022] [Indexed: 01/05/2023] Open
Abstract
Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.
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22
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Liu R, Luo X, Li J, Lei Y, Zeng F, Huang X, Lan Y, Yang F. Melatonin: A window into the organ-protective effects of sepsis. Biomed Pharmacother 2022; 154:113556. [PMID: 35994818 DOI: 10.1016/j.biopha.2022.113556] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/22/2022] [Accepted: 08/14/2022] [Indexed: 11/02/2022] Open
Abstract
Sepsis is an uncontrolled host response to infection. In some cases, it progresses to multi-organ insufficiency, leading to septic shock and increased risk of mortality. Various organ support strategies are currently applied clinically, but they are still inadequate in terms of reducing mortality. Melatonin is a hormone that regulates sleep and wakefulness, and it is associated with a reduced risk of death in patients with sepsis. Evidence suggests that melatonin may help protect organ function from sepsis-related damage. Here, we review information related to the role of melatonin in protecting organ function during sepsis and explore its potential clinical applications, with the aim of providing an effective therapeutic strategy for treating sepsis-induced organ insufficiency.
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Affiliation(s)
- Rongan Liu
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaoxiu Luo
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jiajia Li
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yu Lei
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Fan Zeng
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaobo Huang
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yunping Lan
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
| | - Fuxun Yang
- Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
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23
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Taher A, Shokoohmand F, Abdoli E, Mohammadi Y, Mehrpooya M. A pilot study on the melatonin treatment in patients with early septic shock: results of a single-center randomized controlled trial. Ir J Med Sci 2022; 191:1913-1924. [PMID: 34468959 PMCID: PMC8408361 DOI: 10.1007/s11845-021-02758-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/25/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND We assessed the potential impact of a high dose of melatonin treatment in patients with early septic shock. METHODS Forty patients with early septic shock were randomly allocated to the melatonin or placebo groups. Besides standard-of-care treatment, melatonin and placebo were administered at a dose of 50 mg for five consecutive nights. The efficacy outcomes were severity of organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score, the number of patients requiring mechanical ventilation and ventilator-free days, the mean required vasopressor dose and vasopressor-free days, and 28 days all-cause mortality. RESULTS After 5-day treatment, the mean SOFA scores decreased 4.05 ± 4.75 score in the melatonin group and 2.25 ± 4.87 in the placebo group. On day 28, 60% of the melatonin-treated patients and 35% of the placebo-treated patients had a SOFA score below six. Thirteen cases in the placebo group and nine cases in the melatonin group required mechanical ventilation; however, there was no statistically significant difference between the groups regarding these outcomes. The melatonin-treated patients had more ventilator-free days than placebo-treated patients over the 28-day (16.90 ± 9.24 vs. 10.00 ± 10.94; p value = 0.035). The mean reduction in the required dose of vasopressor was 6.2 ± 5.12 in the melatonin-treated patients compared to 3.20 ± 3.95 in the placebo-treated patients (p value = 0.045). Vasopressor-free days in the melatonin-treated group were also significantly more than the placebo-treated group (12.75 ± 7.43 days vs. 10.15 ± 6.12 days; p value = 0.046). CONCLUSIONS Our pilot study supported the potential benefits of melatonin in treating septic shock. Further clinical evidence is required for expanding and confirming these findings. TRIAL REGISTRATION The trial was registered at Clinicaltrials.gov (ID code: IRCT20120215009014N296). Registration date: 15/09/2019.
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Affiliation(s)
- Abbas Taher
- Department of Anesthesiology and Critical Care, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farnaz Shokoohmand
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Elham Abdoli
- Department of Infectious Disease, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Younes Mohammadi
- Modeling of Noncommunicable Diseases Research Center, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Mehrpooya
- Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
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24
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Martimbianco ALC, Pacheco RL, Bagattini ÂM, de Fátima Carreira Moreira Padovez R, Azevedo LCP, Riera R. Vitamin C-based regimens for sepsis and septic shock: Systematic review and meta-analysis of randomized clinical trials. J Crit Care 2022; 71:154099. [PMID: 35763993 DOI: 10.1016/j.jcrc.2022.154099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 02/16/2022] [Accepted: 06/13/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE to critically appraise and synthesize the evidence on the effects of vitamin C-based regimens for patients with sepsis or septic shock. METHODS a broad search was performed on May 2021 to identify randomized clinical trials (RCTs) assessing vitamin C-based regimens as adjuvant therapy for adults with sepsis or septic shock. We used the Cochrane Risk of Bias table to assess the methodological quality of the included RCTs and the GRADE approach to evaluate the evidence certainty. RESULTS We included 20 RCTs (2124 participants). Evidence from low to very low certainty showed that vitamin C compared to placebo may reduce all-cause mortality up to 28 days (relative risk [RR] 0.60, 95% confidence interval (CI) 0.45 to 0.80, 4 RCTs, 335 participants). Considering the other comparisons (vitamin C alone or combined with thiamine and/or hydrocortisone, compared to placebo, standard care or hydrocortisone), there were a little to no difference or very uncertain evidence for adverse events, SOFA score, ICU length of stay, acute kidney injury, mechanical ventilation- and vasoactive drugs-free days up to 28 days. CONCLUSION Further RCTs with higher methodological quality, an increased number of participants and assessing clinically relevant outcomes are needed to provide better decision-making guidance. PROSPERO REGISTER CRD42021251786.
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Affiliation(s)
- Ana Luiza Cabrera Martimbianco
- Hospital Sírio-Libanês (HSL), São Paulo, SP, Brazil; Universidade Metropolitana de Santos (Unimes), Santos, SP, Brazil; Oxford-Brazil EBM Alliance, Brazil
| | - Rafael Leite Pacheco
- Hospital Sírio-Libanês (HSL), São Paulo, SP, Brazil; Oxford-Brazil EBM Alliance, Brazil; Centro Universitário São Camilo (CUSC), São Paulo, SP, Brazil; Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brazil.
| | | | | | | | - Rachel Riera
- Hospital Sírio-Libanês (HSL), São Paulo, SP, Brazil; Oxford-Brazil EBM Alliance, Brazil; Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brazil
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25
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Grudlewska-Buda K, Wiktorczyk-Kapischke N, Budzyńska A, Kwiecińska-Piróg J, Przekwas J, Kijewska A, Sabiniarz D, Gospodarek-Komkowska E, Skowron K. The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus? Antioxidants (Basel) 2022; 11:antiox11071247. [PMID: 35883738 PMCID: PMC9312329 DOI: 10.3390/antiox11071247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/21/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading worldwide. For this reason, new treatment methods are constantly being researched. Consequently, new and already-known preparations are being investigated to potentially reduce the severe course of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection induces the production of pro-inflammatory cytokines and acute serum biomarkers in the host organism. In addition to antiviral drugs, there are other substances being used in the treatment of COVID-19, e.g., those with antioxidant properties, such as vitamin C (VC). Exciting aspects of the use of VC in antiviral therapy are its antioxidant and pro-oxidative abilities. In this review, we summarized both the positive effects of using VC in treating infections caused by SARS-CoV-2 in the light of the available research. We have tried to answer the question as to whether the use of high doses of VC brings the expected benefits in the treatment of COVID-19 and whether such treatment is the correct therapeutic choice. Each case requires individual assessment to determine whether the positives outweigh the negatives, especially in the light of populational studies concerning the genetic differentiation of genes encoding the solute carriers responsible forVC adsorption. Few data are available on the influence of VC on the course of SARS-CoV-2 infection. Deducing from already-published data, high-dose intravenous vitamin C (HDIVC) does not significantly lower the mortality or length of hospitalization. However, some data prove, among other things, its impact on the serum levels of inflammatory markers. Finally, the non-positive effect of VC administration is mainly neutral, but the negative effect is that it can result in urinary stones or nephropathies.
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Affiliation(s)
- Katarzyna Grudlewska-Buda
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
| | - Natalia Wiktorczyk-Kapischke
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
| | - Anna Budzyńska
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
| | - Joanna Kwiecińska-Piróg
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
| | - Jana Przekwas
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
| | - Agnieszka Kijewska
- Department of Immunobiology and Environmental Biology, Institute of Maritime and Tropical Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland;
| | | | - Eugenia Gospodarek-Komkowska
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
| | - Krzysztof Skowron
- Department of Microbiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (K.G.-B.); (N.W.-K.); (A.B.); (J.K.-P.); (J.P.); (E.G.-K.)
- Correspondence: ; Tel.: +48-(52)-585-38-38
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26
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Kozlov AV, Grillari J. Pathogenesis of Multiple Organ Failure: The Impact of Systemic Damage to Plasma Membranes. Front Med (Lausanne) 2022; 9:806462. [PMID: 35372390 PMCID: PMC8964500 DOI: 10.3389/fmed.2022.806462] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 02/09/2022] [Indexed: 11/19/2022] Open
Abstract
Multiple organ failure (MOF) is the major cause of morbidity and mortality in intensive care patients, but the mechanisms causing this severe syndrome are still poorly understood. Inflammatory response, tissue hypoxia, immune and cellular metabolic dysregulations, and endothelial and microvascular dysfunction are the main features of MOF, but the exact mechanisms leading to MOF are still unclear. Recent progress in the membrane research suggests that cellular plasma membranes play an important role in key functions of diverse organs. Exploration of mechanisms contributing to plasma membrane damage and repair suggest that these processes can be the missing link in the development of MOF. Elevated levels of extracellular phospholipases, reactive oxygen and nitrogen species, pore-forming proteins (PFPs), and dysregulation of osmotic homeostasis occurring upon systemic inflammatory response are the major extracellular inducers of plasma membrane damage, which may simultaneously operate in different organs causing their profound dysfunction. Hypoxia activates similar processes, but they predominantly occur within the cells targeting intracellular membrane compartments and ultimately causing cell death. To combat the plasma membrane damage cells have developed several repair mechanisms, such as exocytosis, shedding, and protein-driven membrane remodeling. Analysis of knowledge on these mechanisms reveals that systemic damage to plasma membranes may be associated with potentially reversible MOF, which can be quickly recovered, if pathological stimuli are eliminated. Alternatively, it can be transformed in a non-resolving phase, if repair mechanisms are not sufficient to deal with a large damage or if the damage is extended to intracellular compartments essential for vital cellular functions.
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Affiliation(s)
- Andrey V Kozlov
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation With AUVA, LBG, Vienna, Austria.,Austrian Cluster for Tissue Regeneration, Medical University of Vienna, Vienna, Austria.,Laboratory of Navigational Redox Lipidomics and Department of Human Pathology, IM Sechenov Moscow State Medical University, Vienna, Austria
| | - Johannes Grillari
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation With AUVA, LBG, Vienna, Austria.,Austrian Cluster for Tissue Regeneration, Medical University of Vienna, Vienna, Austria.,Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria
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27
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Sepsis: New Challenges and Future Perspectives for an Evolving Disease—Precision Medicine Is the Way! Medicina (B Aires) 2021; 57:medicina57101109. [PMID: 34684146 PMCID: PMC8538484 DOI: 10.3390/medicina57101109] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 10/13/2021] [Indexed: 11/20/2022] Open
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28
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Steroid, ascorbic acid, and thiamine in adults with sepsis and septic shock: a systematic review and component network meta-analysis. Sci Rep 2021; 11:15777. [PMID: 34349184 PMCID: PMC8338943 DOI: 10.1038/s41598-021-95386-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 07/26/2021] [Indexed: 02/07/2023] Open
Abstract
To assess the effect from individual component in combinations of steroid, ascorbic acid, and thiamine on outcomes in adults with sepsis and septic shock with component network meta-analysis (NMA). We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials from 1980 to March 2021 for randomized controlled trials (RCT) that studied the use of glucocorticoid, fludrocortisone, ascorbic acid, and thiamine in patients with sepsis and septic shock. Citations screening, study selection, data extraction, and risk of bias assessment were independently performed by two authors. The primary outcome was short-term mortality. Secondary outcomes were longer-term mortality, time to resolution of shock and duration of mechanical ventilation. Thirty-three RCTs including 9898 patients presented on short-term mortality. In additive component NMA, patients on ascorbic acid alone (RR 0.74, 95% CI 0.57-0.97) or the combination of glucocorticoid and fludrocortisone (RR 0.89, 95% CI 0.80-0.99) had lower short-term mortality, but only the latter was associated with improved long-term mortality (RR 0.89, 95% CI 0.82-0.98). The use of glucocorticoid or the combination of glucocorticoid, ascorbic acid and thiamine hastened resolution of shock. Component NMA showed glucocorticoid (MD - 0.96, 95% CI - 1.61 to - 0.30) but not ascorbic acid or thiamine shortened the time to resolution of shock. Glucocorticoid shortened the duration of mechanical ventilation (MD - 1.48, 95% CI - 2.43 to - 0.52). In adults with sepsis and septic shock, the combination of glucocorticoid and fludrocortisone improved short-term and longer-term mortality. Glucocorticoid shortened the time to resolution of shock and duration of mechanical ventilation. There was no strong evidence supporting the routine use of thiamine and ascorbic acid, but they were associated with minimal adverse effects.
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29
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O'Connor KM, Ashoori M, Dias ML, Dempsey EM, O'Halloran KD, McDonald FB. Influence of innate immune activation on endocrine and metabolic pathways in infancy. Am J Physiol Endocrinol Metab 2021; 321:E24-E46. [PMID: 33900849 DOI: 10.1152/ajpendo.00542.2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Prematurity is the leading cause of neonatal morbidity and mortality worldwide. Premature infants often require extended hospital stays, with increased risk of developing infection compared with term infants. A picture is emerging of wide-ranging deleterious consequences resulting from innate immune system activation in the newborn infant. Those who survive infection have been exposed to a stimulus that can impose long-lasting alterations into later life. In this review, we discuss sepsis-driven alterations in integrated neuroendocrine and metabolic pathways and highlight current knowledge gaps in respect of neonatal sepsis. We review established biomarkers for sepsis and extend the discussion to examine emerging findings from human and animal models of neonatal sepsis that propose novel biomarkers for early identification of sepsis. Future research in this area is required to establish a greater understanding of the distinct neonatal signature of early and late-stage infection, to improve diagnosis, curtail inappropriate antibiotic use, and promote precision medicine through a biomarker-guided empirical and adjunctive treatment approach for neonatal sepsis. There is an unmet clinical need to decrease sepsis-induced morbidity in neonates, to limit and prevent adverse consequences in later life and decrease mortality.
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Affiliation(s)
- K M O'Connor
- Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland
| | - M Ashoori
- Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland
- Irish Centre for Maternal and Child Health Research (INFANT), University College Cork, Cork, Ireland
| | - M L Dias
- Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland
| | - E M Dempsey
- Irish Centre for Maternal and Child Health Research (INFANT), University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, School of Medicine, College of Medicine and Health, Cork University Hospital, Wilton, Cork, Ireland
| | - K D O'Halloran
- Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland
- Irish Centre for Maternal and Child Health Research (INFANT), University College Cork, Cork, Ireland
| | - F B McDonald
- Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland
- Irish Centre for Maternal and Child Health Research (INFANT), University College Cork, Cork, Ireland
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30
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Rodríguez-Fierros FL, Guarner-Lans V, Soto ME, Manzano-Pech L, Díaz-Díaz E, Soria-Castro E, Rubio-Ruiz ME, Jiménez-Trejo F, Pérez-Torres I. Modulation of Renal Function in a Metabolic Syndrome Rat Model by Antioxidants in Hibiscus sabdariffa L. Molecules 2021; 26:molecules26072074. [PMID: 33916540 PMCID: PMC8038460 DOI: 10.3390/molecules26072074] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 12/16/2022] Open
Abstract
Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.
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Affiliation(s)
- Félix Leao Rodríguez-Fierros
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico; (F.L.R.-F.); (L.M.-P.); (E.S.-C.)
| | - Verónica Guarner-Lans
- Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico; (V.G.-L.); (M.E.R.-R.)
| | - María Elena Soto
- Department of Immunology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico;
| | - Linaloe Manzano-Pech
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico; (F.L.R.-F.); (L.M.-P.); (E.S.-C.)
| | - Eulises Díaz-Díaz
- Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Sección XVI, Tlalpan, Mexico City 14000, Mexico;
| | - Elizabeth Soria-Castro
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico; (F.L.R.-F.); (L.M.-P.); (E.S.-C.)
| | - María Esther Rubio-Ruiz
- Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico; (V.G.-L.); (M.E.R.-R.)
| | - Francisco Jiménez-Trejo
- Department of Reproductive Biology, Instituto Nacional de Pediatría, Insurgentes Sur No. 3700-C, Coyoacán, Mexico City 04530, Mexico;
| | - Israel Pérez-Torres
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico; (F.L.R.-F.); (L.M.-P.); (E.S.-C.)
- Correspondence: or ; Tel.: +52-5573-2911 (ext. 25203); Fax: +52-5573-0926
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Effect of N-Acetylcysteine Administration on 30-Day Mortality in Critically Ill Patients with Septic Shock Caused by Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii: A Retrospective Case-Control Study. Antibiotics (Basel) 2021; 10:antibiotics10030271. [PMID: 33800296 PMCID: PMC8001571 DOI: 10.3390/antibiotics10030271] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/03/2021] [Accepted: 03/05/2021] [Indexed: 01/02/2023] Open
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab) represent important cause of severe infections in intensive care unit (ICU) patients. N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties, showing also in-vitro antibacterial activity. Aim was to evaluate the effect on 30-day mortality of the addition of intravenous NAC to antibiotics in ICU patients with CR-Kp or CR-Ab septic shock. A retrospective, observational case:control study (1:2) in patients with septic shock caused by CR-Kp or CR-Ab hospitalized in two different ICUs was conducted. Cases included patients receiving NAC plus antimicrobials, controls included patients not receiving NAC. Cases and controls were matched for age, SAPS II, causative agent and source of infection. No differences in age, sex, SAPS II score or time to initiate definitive therapy were observed between cases and controls. Pneumonia and bacteremia were the leading infections. Overall, mortality was 48.9% (33.3% vs. 56.7% in cases and controls, p = 0.05). Independent risk factors for mortality were not receiving NAC (p = 0.002) and CR-Ab (p = 0.034) whereas therapy with two in-vitro active antibiotics (p = 0.014) and time to initial definite therapy (p = 0.026) were protective. NAC plus antibiotics might reduce the 30-day mortality rate in ICU patients with CR-Kp and CR-Ab septic shock.
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Chavarría AP, Vázquez RRV, Cherit JGD, Bello HH, Suastegui HC, Moreno-Castañeda L, Alanís Estrada G, Hernández F, González-Marcos O, Saucedo-Orozco H, Manzano-Pech L, Márquez-Velasco R, Guarner-Lans V, Pérez-Torres I, Soto ME. Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19. Comput Struct Biotechnol J 2021; 19:1379-1390. [PMID: 33680348 PMCID: PMC7910139 DOI: 10.1016/j.csbj.2021.02.009] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/01/2021] [Accepted: 02/16/2021] [Indexed: 01/08/2023] Open
Abstract
The type 2 coronavirus causes severe acute respiratory syndrome (SARS-CoV-2) and produces pneumonia with pulmonary alveolar collapse. In some cases it also causes sepsis and septic shock. There is no specific treatment for coronavirus disease 2019 (COVID-19). Vitamin C (Vit C), Vitamin E (Vit E), N-acetylcysteine (NAC) and Melatonin (MT) increase the intracellular content of GSH, kidnap free radicals and protect DNA, proteins in the cytosol and lipids in cell membranes. Pentoxifylline (Px) has anti-inflammatory activities. Here we evaluate the effect of Vit C, Vit E, NAC, and MT plus Px in COVID-19 patients with moderate and severe pneumonia. 110 patients of either sex were included. They were divided into five groups with 22 patients each. Group 1 received Vit C + Px, group 2 Vit E + Px, group 3 NAC + Px, group 4 MT + Px, and group 5 only Px. Oxidative stress (OS) markers such as lipid peroxidation (LPO) levels, total antioxidant capacity (TAC) and nitrites (NO2 -) were evaluated in plasma. The antioxidant therapy improved the survival scores including the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and chronic Health Evaluation II (Apache II), the Simplified Acute Physiology Score II (SAPS II), the Critical Illness Risk Score, Launched during COVID-19 crisis (COVIDGRAM) and the Glasgow Coma Scale (GCS). We found that LPO (p≤0.04) and inflammation markers such as interleukin-6 (IL-6, p≤ 0.01), C reactive protein (CRP, p ≤ 0.01) and procalcitonin (PCT, p ≤ 0.05) were elevated. TAC (p ≤ 0.03) and NO2 - (p ≤ 0.04) found themselves diminished in diminished in COVID-19 patients upon admission to the hospital. The different antioxidants reversed this alteration at the end of the treatment. The treatment with antioxidant supplements such as Vit C, E, NAC, and MT plus Px could decelerate the aggressive and lethal development of COVID-19. Antioxidant therapy can be effective in this pandemia since it improves the survival scores including SOFA, Apache II, SAPS II, COVIDGRAM, GCS by lowering the LPO, IL-6, CRP, PCT and increasing systemic TAC and NO2 -.
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Affiliation(s)
- Adrián Palacios Chavarría
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
- Critical Care in American British Cowdray (ABC) Medical Center, I.A.P. ABC I.A.P. ABC Sur 136 No. 116 Col. Las Américas, México City 01120 , Mexico
| | - Rafael Ricardo Valdez Vázquez
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - José Guillermo Domínguez Cherit
- Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” Vasco de Quiroga 15, Sección XVI, Tlalpan, México City 14000, Mexico
- Tecnológico de Monterrey EMCS, Mexico
| | - Héctor Herrera Bello
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - Humberto Castillejos Suastegui
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - Lidia Moreno-Castañeda
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - Gabriela Alanís Estrada
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - Fabián Hernández
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - Omar González-Marcos
- Critical Care Unit of the Temporal COVID-19 Unit, Citibanamex Center Av. del Conscripto 311, Lomas de Sotelo, Hipódromo de las Américas, Miguel Hidalgo, 11200 Ciudad de México, CDMX, Mexico
| | - Huitzilihuitl Saucedo-Orozco
- Cardioneumology Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico
- Cardioneumology Department, Centro Médico Nacional La Raza Instituto Mexicano del Seguro Social Seris y Zaachila, Col. La Raza Azcapotzalco, 02990 Ciudad de México, CDMX, Mexico
| | - Linaloe Manzano-Pech
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez. Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Ricardo Márquez-Velasco
- Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez. Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Verónica Guarner-Lans
- Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez. Badiano 1, Sección XVI, Tlalpan, México City 14080 Mexico
| | - Israel Pérez-Torres
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez. Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
| | - Maria Elena Soto
- Department of Immunology , Instituto Nacional de Cardiología Ignacio Chávez. Juan Badiano 1 , Sección XVI , Tlalpan , México City 14080 , Mexico
- American British Cowdray (ABC) Medical Center , I.A.P. ABC I.A.P. ABC Sur 136 No. 116 Col. Las Américas , México City 01120 , Mexico
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