Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system

Abstract Background Ketoconazole (KET) is a broad-spectrum antifungal drug that has been reported to induce hepatotoxicity in humans and animals. Methods The safe guarding response of Gentiana extract (GEN) against KET-induced hepatotoxicity was investigated in this study using male Wistar rats. GEN...

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Main Authors: Alaaeldin Ahmed Hamza, Mona Gamel, Ali Abdalla, Youssef Abdalla, Amr Amin
Format: Article
Language:English
Published: SpringerOpen 2023-01-01
Series:Journal of Basic and Applied Zoology
Subjects:
Online Access:https://doi.org/10.1186/s41936-022-00321-7
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author Alaaeldin Ahmed Hamza
Mona Gamel
Ali Abdalla
Youssef Abdalla
Amr Amin
author_facet Alaaeldin Ahmed Hamza
Mona Gamel
Ali Abdalla
Youssef Abdalla
Amr Amin
author_sort Alaaeldin Ahmed Hamza
collection DOAJ
description Abstract Background Ketoconazole (KET) is a broad-spectrum antifungal drug that has been reported to induce hepatotoxicity in humans and animals. Methods The safe guarding response of Gentiana extract (GEN) against KET-induced hepatotoxicity was investigated in this study using male Wistar rats. GEN ethanol extract was orally administered to rats (1 g/kg b.wt) for 30 days. Beginning on day 26, KET was intraperitoneally administered once daily for 5 days using a dose of 100 mg/kg. The hepatoprotective effects of GEN against liver damage induced by KET were monitored through significant decrements in serum levels of aminotransferase and alpha-fetoprotein as well as recorded hepatic histopathological changes. Results The hepatotoxicity of KET treatment was accompanied with a marked oxidative damage to hepatic proteins, lipids, and DNA, and depletions in natural antioxidants (glutathione and superoxide dismutase). GEN inhibited KET-induced oxidative stress by diminishing lipid peroxidation, protein carbonylation, and oxidative stress in DNA. These free radical mediated effects were greatly decreased with GEN treatment. Conclusions This study suggests that GEN’s hepatoprotective effects could be attributed to its antioxidant properties.
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spelling doaj.art-b9e3b9739ecd4d9d8f33f5384fae68082023-01-08T12:17:35ZengSpringerOpenJournal of Basic and Applied Zoology2090-990X2023-01-0184111210.1186/s41936-022-00321-7Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense systemAlaaeldin Ahmed Hamza0Mona Gamel1Ali Abdalla2Youssef Abdalla3Amr Amin4Hormone Evaluation Department, National Organization for Drug Control and ResearchHormone Evaluation Department, National Organization for Drug Control and ResearchDepartment of Health Sciences, Weinberg Institute for Cognitive Science, University of MichiganDepartment of Kinesiology, Michigan State UniversityBiology Department, UAE UniversityAbstract Background Ketoconazole (KET) is a broad-spectrum antifungal drug that has been reported to induce hepatotoxicity in humans and animals. Methods The safe guarding response of Gentiana extract (GEN) against KET-induced hepatotoxicity was investigated in this study using male Wistar rats. GEN ethanol extract was orally administered to rats (1 g/kg b.wt) for 30 days. Beginning on day 26, KET was intraperitoneally administered once daily for 5 days using a dose of 100 mg/kg. The hepatoprotective effects of GEN against liver damage induced by KET were monitored through significant decrements in serum levels of aminotransferase and alpha-fetoprotein as well as recorded hepatic histopathological changes. Results The hepatotoxicity of KET treatment was accompanied with a marked oxidative damage to hepatic proteins, lipids, and DNA, and depletions in natural antioxidants (glutathione and superoxide dismutase). GEN inhibited KET-induced oxidative stress by diminishing lipid peroxidation, protein carbonylation, and oxidative stress in DNA. These free radical mediated effects were greatly decreased with GEN treatment. Conclusions This study suggests that GEN’s hepatoprotective effects could be attributed to its antioxidant properties.https://doi.org/10.1186/s41936-022-00321-7GentianKetoconazoleHepatic injuryProtection
spellingShingle Alaaeldin Ahmed Hamza
Mona Gamel
Ali Abdalla
Youssef Abdalla
Amr Amin
Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
Journal of Basic and Applied Zoology
Gentian
Ketoconazole
Hepatic injury
Protection
title Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
title_full Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
title_fullStr Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
title_full_unstemmed Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
title_short Gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
title_sort gentiana lutea attenuates hepatotoxicity induced by ketoconazole in rats by fortifying the cellular antioxidant defense system
topic Gentian
Ketoconazole
Hepatic injury
Protection
url https://doi.org/10.1186/s41936-022-00321-7
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