Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations

Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kid...

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Main Authors: Shubhangi Gumbar, Sudeep Bhardwaj, Sidharth Mehan, Zuber Khan, Acharan S. Narula, Reni Kalfin, Shams Tabrez, Torki A. Zughaibi, Samina Wasi
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1218506/full
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author Shubhangi Gumbar
Sudeep Bhardwaj
Sidharth Mehan
Zuber Khan
Acharan S. Narula
Reni Kalfin
Reni Kalfin
Shams Tabrez
Shams Tabrez
Torki A. Zughaibi
Torki A. Zughaibi
Samina Wasi
author_facet Shubhangi Gumbar
Sudeep Bhardwaj
Sidharth Mehan
Zuber Khan
Acharan S. Narula
Reni Kalfin
Reni Kalfin
Shams Tabrez
Shams Tabrez
Torki A. Zughaibi
Torki A. Zughaibi
Samina Wasi
author_sort Shubhangi Gumbar
collection DOAJ
description Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys.Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers.Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis.Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA’s antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes.Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA’s potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques.
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spelling doaj.art-6382b7e36fb546919db744283c2b04502023-07-13T13:02:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-07-011410.3389/fphar.2023.12185061218506Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterationsShubhangi Gumbar0Sudeep Bhardwaj1Sidharth Mehan2Zuber Khan3Acharan S. Narula4Reni Kalfin5Reni Kalfin6Shams Tabrez7Shams Tabrez8Torki A. Zughaibi9Torki A. Zughaibi10Samina Wasi11Department of Pharmacology, Seth G. L. Bihani S. D. College of Technical Education, Institute of Pharmaceutical Sciences and Drug Research, Sri Ganganagar, Rajasthan, IndiaDepartment of Pharmacology, Seth G. L. Bihani S. D. College of Technical Education, Institute of Pharmaceutical Sciences and Drug Research, Sri Ganganagar, Rajasthan, IndiaDepartment of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga, Punjab, IndiaDepartment of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga, Punjab, IndiaNarula Research, LLC, Chapel Hill, NC, United StatesInstitute of Neurobiology, Bulgarian Academy of Sciences, Sofia, BulgariaDepartment of Healthcare, South-West University “NeofitRilski”, Blagoevgrad, BulgariaKing Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaKing Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, Alkhobar, Saudi ArabiaBackground: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys.Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers.Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis.Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA’s antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes.Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA’s potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques.https://www.frontiersin.org/articles/10.3389/fphar.2023.1218506/fullnephrotoxicitymitochondrial dysfunctionantioxidantgymnemic acidnephroprotection
spellingShingle Shubhangi Gumbar
Sudeep Bhardwaj
Sidharth Mehan
Zuber Khan
Acharan S. Narula
Reni Kalfin
Reni Kalfin
Shams Tabrez
Shams Tabrez
Torki A. Zughaibi
Torki A. Zughaibi
Samina Wasi
Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations
Frontiers in Pharmacology
nephrotoxicity
mitochondrial dysfunction
antioxidant
gymnemic acid
nephroprotection
title Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations
title_full Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations
title_fullStr Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations
title_full_unstemmed Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations
title_short Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations
title_sort renal mitochondrial restoration by gymnemic acid in gentamicin mediated experimental nephrotoxicity evidence from serum kidney and histopathological alterations
topic nephrotoxicity
mitochondrial dysfunction
antioxidant
gymnemic acid
nephroprotection
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1218506/full
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