Troglitazone induces a rapid drop of mitochondrial membrane potential in liver HepG2 cells.
Toxicol Lett
; 155(1): 41-50, 2005 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-15585358
ABSTRACT
Troglitazone, a thiazolidinedione containing compound, was widely used to treat non-insulin dependent-diabetes. Unfortunately, troglitazone was associated with a sporadic liver toxicity that led to a cessation of its use clinically. Here we show that troglitazone induces a rapid and dose-dependent drop of mitochondrial membrane potential in liver HepG2 cells. The decrease in mitochondrial membrane potential induced by 100 microM troglitazone was completed after 5 min and similar in magnitude to that caused by carbonyl cyanide m-chloro phenylhydrazone. The troglitazone-induced loss of mitochondrial membrane potential preceded changes in cell permeability and cell count. In addition, troglitazone-induced a rise of intracellular calcium, subsequent to the drop in mitochondrial membrane potential, which was blocked by EGTA and the Na+/Ca2+ exchange inhibitor bepridil. Finally, application of 100 microM troglitazone for 24h to HepG2 cells resulted in activation of caspase 3. The results of this study shed light on the molecular mechanisms by which troglitazone can cause cytotoxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mitocôndrias Hepáticas
/
Cromanos
/
Tiazolidinedionas
/
Hipoglicemiantes
Limite:
Humans
Idioma:
En
Revista:
Toxicol Lett
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos