Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Effect of P-450 Inducers on Glutathione (GSH) Depletion by Bromobenzene in Primary Cultures of Dog Hepatocytes
Toshio HARAUCHIMasaharu HIRATA
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1994 Volume 17 Issue 5 Pages 658-661

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Abstract

Primary cultures of dog hepatocytes sensitively responded to various inducers of cytochrome P-450 ; phenobarbital (PB) significantly elevated the activity of 7-ethoxycoumarin O-deethylase (ECOD) and progesterone 6β-hydroxylase (6β-OHP). β-Naphthoflavone (β-NF) and rifampicin (Rif) elevated the levels of 7-ethoxyresorufin O-deethylase (EROD) and 6β-OHP, respectively. When primary cultures of dog hepatocytes were incubated with bromobenzene, cellular reduced glutathione (GSH) levels decreased time-and dose-dependently. Pretreatment of the cultures with PB enhanced GSH depletion by bromobenzene, while β-NF and Rif had little effect, suggesting that the 2B type cytochrome P-450 is responsible for the primary oxidation of bromobenzene to GSH-reactive metabolite (s). Bromobenzene-dependent GSH depletion was completely prevented by 10 μM SKF-525A both in the control and PB-treated primary cultures. Treatment of dog primary cultures with PB analogues also elevated the level of drug-metabolizing activity leading the cells to be more susceptible to GSH depletion by bromobenzene.

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