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Effects of chlorobenzene-induced alteration in glutathione levels on cysteine metabolism in rat liver were investigated. Male Wistar rats were intraperitoneally injected with chlorobenzene (0.2, 0.5, 1.0 or 2.0 mmol/kg body weight). Both hepatic glutathione and cysteine levels were dose-dependently decreased by the chlorobenzene 6 h after the injection. However, at 24 h, the glutathione in the rats with chlorobenzene increased significantly as compared to that in the rats without chlorobenzene. Concomitant to the elevation in glutathione levels, hepatic glutathione synthesis activities were increased by the chlorobenzene by 68-111%. On the other hand, no significant difference between the rats with and without chlorobenzene was observed as regards cysteine levels at 24 h. Hepatic glutamate, glycine, methionine and serine levels were unaltered but hepatic taurine levels were significantly decreased by the chlorobenzene at both 6 and 24 h. Chlorobenzene administration had no effect on hepatic cystathionine synthase and cystathionase activities. These results indicate that a transient loss of hepatic glutathione, caused by the administration of chlorobenzene, resulted in an acceleration of glutathione synthesis and an increase of cysteine demand in the liver.

Variation of cysteine level by chlorobenzene-induced pertubation of glutathione metabolism in rat liver.