The relationship between diphenylamine structure and NSAIDs-induced hepatocytes injury.
Toxicol Lett
; 186(2): 111-4, 2009 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-19429231
ABSTRACT
OBJECTIVE:
Many nonsteroidal anti-inflammatory drugs (NSAIDs) with diphenylamine structure induce severe hepatotoxicities. We evaluated the role of diphenylamine structure in liver injuries induced by these NSAIDs.METHODS:
Effects of diphenylamine, diclofenac and tolfenamic acid on mitochondrial permeability transition (MPT) and efflux of calcium in isolated liver mitochondria as well as on cellular ATP content and mitochondrial membrane depolarization in rat primary hepatocyte cultures were examined.RESULTS:
Diclofenac and tolfenamic acid induced cyclosporine A (CsA)-sensitive mitochondrial swelling and membrane depolarization in isolated liver mitochondria. Only diclofenac caused the release of calcium in isolated liver mitochondria. Diphenylamine had no effects on isolated liver mitochondria. All three compounds decreased ATP content and induced mitochondrial membrane depolarization. CsA attenuated these effects, suggesting MPT might be involved in the hepatotoxicities caused by diphenylamine, diclofenac and tolfenamic acid. SKF-525A, a general inhibitor of CYP450, markedly inhibited the injury induced by diphenylamine, but not diclofenac or tolfenamic acid.CONCLUSION:
The hepatotoxicities caused by diclofenac and tolfenamic acid may be attributed to the mitochondrial dysfunction induced by these drugs instead of the diphenylamine structure per se.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
/
Hepatócitos
/
Difenilamina
/
Doença Hepática Induzida por Substâncias e Drogas
Limite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
China