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Mitochondrial Dysfunction as a Mechanism for Pioglitazone-Induced Injury toward HepG2 Cell Line
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نویسنده
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Niknahad Hossein ,Heidari Reza ,Alzuhairi Mohammad Abdolsalam ,Najibi Najibi
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منبع
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pharmaceutical sciences - 2015 - دوره : 20 - شماره : 4 - صفحه:169 -174
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چکیده
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Background: thiazolidinediones (tzds) are widely used for treatment of type iidiabetes mellitus in humans. the first drug of this class, troglitazone, was withdrawnfrom the market due to a high incidence of hepatotoxicity. several cases of liver injuryinduced by other tzds such as pioglitazone is also reported. the mechanism ofcellular injury induced by pioglitazone is not recognized precisely so far.mitochondria is a postulated target for tzds to induce injury. methods: thisinvestigation was designed to evaluate the cytotoxic effects of pioglitazone in culturedhepg2 cells. cell death, glutathione level, occurrence of lipid peroxidation, andfinally cellular adenosine triphosphate (atp) content, as an index of mitochondrialfunctionality, were monitored in hepg2 cells after pioglitazone administration.results: it was found that pioglitazone was toxic towards hepg2 cells concentrationdependently and 1 mm of pioglitazone reduced cellular viability to less than 60% in48 hours of incubation. pioglitazone administration reduced atp content of the cells,but did not induce oxidative stress in this cell line, as no lipid peroxidation and/ordecrease in cellular glutathione were detected. administration of atp suppliersdihydroxyacetone (5 and 10 mm) and glyceraldehyde (1 and 5 mm), inhibited drop incellular atp induced by pioglitazone and prevented drug-induced cell death.conclusion: these results suggest that pioglitazone affect cellular mitochondria andmight cause cytotoxicity by prevention of atp production.
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کلیدواژه
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Hepatotoxicity ,Mitochondrial dysfunction ,Pioglitazone ,Thiazolidinediones
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آدرس
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Shiraz, Shiraz University of Medical Sciences, ایران, Shiraz, Shiraz University of Medical Sciences, ایران, Shiraz, Shiraz University of Medical Sciences, ایران, shiraz university of medical sciences, ایران
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پست الکترونیکی
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asma_najibi @yahoo.com
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Authors
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