H. Thor, S. Svensson, P. Hartzell
1981
Citations
0
Influential Citations
19
Citations
Journal
Advances in experimental medicine and biology
Abstract
Bromobenzene is a widely studied hepatotoxic agent which produces midzonal liver necrosis when administered in sufficient doses to laboratory animals (Koch-Weser et al., 1953; Reid et al., 1971). Metabolic activation of bromobenzene to reactive intermediate(s) by the cytochrome P-450-linked monooxygenase system is required for this agent to produce liver damage which, in turn, is preceded by depletion of hepatic glutathione (GSH) (Jollow et al., 1974; Thor et al., 1978b). Accordingly, the hepatotoxic effect of bromobenzene is enhanced by either induction of the cytochrome P-450 system or lowering of hepatic glutathione level by pretreatment of the animals with GSH-depleting agents. Conversely, hepatotoxicity is prevented by simultaneous administration of cytochrome P-450 inhibitors and is also counteracted by the stimulated glutathione biosynthesis resulting from administration of certain glutathione precursors (Mitchell et al., 1971; Thor et al., 1979).