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Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity
AIMS: Cisplatin (CP), as an effective alkylating agent, is widely used in cancer treatment, while hepatotoxicity is one of its side effects. Gliclazide (GLZ), as an oral hypoglycemic drug, has antioxidant and anti‐inflammatory properties. This study was designed to investigate the protective effect...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130655/ https://www.ncbi.nlm.nih.gov/pubmed/34003600 http://dx.doi.org/10.1002/prp2.788 |
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author | Taghizadeh, Fatemeh Hosseinimehr, Seyed Jalal Zargari, Mehryar Karimpour Malekshah, Abbasali Mirzaei, Mansoureh Talebpour Amiri, Fereshteh |
author_facet | Taghizadeh, Fatemeh Hosseinimehr, Seyed Jalal Zargari, Mehryar Karimpour Malekshah, Abbasali Mirzaei, Mansoureh Talebpour Amiri, Fereshteh |
author_sort | Taghizadeh, Fatemeh |
collection | PubMed |
description | AIMS: Cisplatin (CP), as an effective alkylating agent, is widely used in cancer treatment, while hepatotoxicity is one of its side effects. Gliclazide (GLZ), as an oral hypoglycemic drug, has antioxidant and anti‐inflammatory properties. This study was designed to investigate the protective effect of GLZ against CP‐induced hepatotoxicity in mice. METHODS: In this experimental study, 64 adult male mice randomly were allocated into eight groups (8 mice/group). Control, GLZ (5, 10, and 25 mg/kg, orally), CP (10 mg/kg, single dose, intraperitoneally), and CP+GLZ (in three doses). GLZ was administrated for 10 consecutive days. CP was injected on the 7th day of the study. At the end of the experiment, hepatotoxicity was evaluated by serum and tissue biochemical, histopathological, and immunohistochemical assessments. RESULTS: The data were revealed that CP increased oxidative stress (increased MDA and reduced GSH), liver damage enzymes (ALT, AST, and ALP), and immunoreactivity of caspase‐3 in liver tissue of CP‐injected mice. Also, CP induced histopathological changes such as eosinophilic of hepatocytes, dilatation of sinusoids, congestion, and proliferation of Kupffer cells. GLZ administration significantly ameliorated serum functional enzyme and hepatic oxidative stress markers in CP‐injected mice. In addition, the histological and immunohistochemical alterations were ameliorated in GLZ‐treated mice. Of the three doses, 10 and 25 mg/kg were more effective. CONCLUSIONS: In conclusion, GLZ with its antioxidant, anti‐inflammatory, and anti‐apoptotic activities, can be suggested as a promising drug in the treatment of CP‐induced hepatotoxicity. |
format | Online Article Text |
id | pubmed-8130655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81306552021-05-21 Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity Taghizadeh, Fatemeh Hosseinimehr, Seyed Jalal Zargari, Mehryar Karimpour Malekshah, Abbasali Mirzaei, Mansoureh Talebpour Amiri, Fereshteh Pharmacol Res Perspect Original Articles AIMS: Cisplatin (CP), as an effective alkylating agent, is widely used in cancer treatment, while hepatotoxicity is one of its side effects. Gliclazide (GLZ), as an oral hypoglycemic drug, has antioxidant and anti‐inflammatory properties. This study was designed to investigate the protective effect of GLZ against CP‐induced hepatotoxicity in mice. METHODS: In this experimental study, 64 adult male mice randomly were allocated into eight groups (8 mice/group). Control, GLZ (5, 10, and 25 mg/kg, orally), CP (10 mg/kg, single dose, intraperitoneally), and CP+GLZ (in three doses). GLZ was administrated for 10 consecutive days. CP was injected on the 7th day of the study. At the end of the experiment, hepatotoxicity was evaluated by serum and tissue biochemical, histopathological, and immunohistochemical assessments. RESULTS: The data were revealed that CP increased oxidative stress (increased MDA and reduced GSH), liver damage enzymes (ALT, AST, and ALP), and immunoreactivity of caspase‐3 in liver tissue of CP‐injected mice. Also, CP induced histopathological changes such as eosinophilic of hepatocytes, dilatation of sinusoids, congestion, and proliferation of Kupffer cells. GLZ administration significantly ameliorated serum functional enzyme and hepatic oxidative stress markers in CP‐injected mice. In addition, the histological and immunohistochemical alterations were ameliorated in GLZ‐treated mice. Of the three doses, 10 and 25 mg/kg were more effective. CONCLUSIONS: In conclusion, GLZ with its antioxidant, anti‐inflammatory, and anti‐apoptotic activities, can be suggested as a promising drug in the treatment of CP‐induced hepatotoxicity. John Wiley and Sons Inc. 2021-05-18 /pmc/articles/PMC8130655/ /pubmed/34003600 http://dx.doi.org/10.1002/prp2.788 Text en © 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Taghizadeh, Fatemeh Hosseinimehr, Seyed Jalal Zargari, Mehryar Karimpour Malekshah, Abbasali Mirzaei, Mansoureh Talebpour Amiri, Fereshteh Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity |
title | Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity |
title_full | Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity |
title_fullStr | Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity |
title_full_unstemmed | Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity |
title_short | Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity |
title_sort | alleviation of cisplatin‐induced hepatotoxicity by gliclazide: involvement of oxidative stress and caspase‐3 activity |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130655/ https://www.ncbi.nlm.nih.gov/pubmed/34003600 http://dx.doi.org/10.1002/prp2.788 |
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