Cytotoxicity of paracetamol and 3,5-dihalgenated analogues: Role of cytochrome P450 and formation of GSH conjugates and protein adducts.

J.G.M. Bessems, L.L.P. van Stee, J.N.M. Commandeur, E.J. Groot, N.P.E. Vermeulen

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The effect of 3,5-dihalogenation of paracetamol (PAR) on the cytotoxicity in rat hepatocytes isolated from 13-naphthoflavone pretreated, non-fasted rats, and the role of cytochrome P-450 in this regard, were studied. On incubation, 3,5-difluoro-PAR, 3,5-dichloro-PAR and 3,5-dibromo-PAR, as well as PAR, caused severe leakage of lactate dehydrogenase (LDH) which was preceded by a rapid concentration- and time-dependent depletion of intracellular glutathione (GSH). IC
Original languageEnglish
Pages (from-to)9-19
JournalToxicology in Vitro
Volume11
DOIs
Publication statusPublished - 1997

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