Mitochondrial Dysfunction as a Mechanism for Pioglitazone-Induced Injury toward HepG2 Cell Line
Year: 2014
Type: article
Abstract: Background:
Thiazolidinediones (TZDs) are widely used for
treatment of type II diabetes mellitus in humans. The first drug of this class,
troglitazone, was withdrawn from the market due to a high incidence of
hepatotoxicity. Several cases of liver injury induced by other TZDs such as
pioglitazone is also reported. The mechanism of cellular injury induced by
pioglitazone is not recognized precisely so far. Mitochondria is a postulated
target for TZDs to induce injury. Methods: This
investigation was designed to evaluate the cytotoxic effects of pioglitazone in
cultured HepG2 cells. Cell death, glutathione level, occurrence of lipid
peroxidation, and finally cellular adenosine triphosphate (ATP) content, as an
index of mitochondrial functionality, were monitored in HepG2 cells after
pioglitazone administration. Results: It was found that
pioglitazone was toxic towards HepG2 cells concentration dependently and 1 mM
of pioglitazone reduced cellular viability to less than 60% in 48 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/or decrease in cellular glutathione were detected. Administration of ATP
suppliers dihydroxyacetone (5 and 10 mM) and glyceraldehyde (1 and 5 mM),
inhibited drop in cellular ATP induced by pioglitazone and prevented
drug-induced cell death. Conclusion: These results suggest
that pioglitazone affect cellular mitochondria and might cause cytotoxicity by
prevention of ATP production.
Source: Pharmaceutical Sciences
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2183792933