Responses of hepatic xenobiotic metabolizing enzymes of mouse, rat and guinea-pig to nickel

Abstract

The effects of nickel (Ni) on hepatic monooxygenase activities (aniline 4-hydroxylase, AH; ethylmorphine N-demethylase, EMND; aminopyrine N-demethylase, AMND), cytochrome P-450, cytochrome b5, microsomal haem and reduced glutathione (GSH) levels, and glutathione S-transferase (GST) activities toward several substrates (1, chloro-2-4-dinitrobenzene, CDNB; 1,2 dichloro-4-nitrobenzene, DCNB; ethacrynic acid, EAA) in mice, rats and guinea-pigs were studied. Ni (59.50 mg NiCl2.6H2O/kg, subcutaneously) was administered to the animals 16 hr prior to sacrifice. Ni significantly inhibited AH, EMND, AMND activities, and decreased cytochrome P-450, cytochrome b5 (except in the livers of rats), and microsomal haem levels in the livers of all the animal species examined. However, the depressions were more profound in livers of mice than in those of the other two species. The hepatic GSH level was significantly inhibited in mice whereas no alteration was observed in rats. In guinea-pigs, the hepatic GSH level was significantly increased by Ni. The hepatic GST activity toward the substrate CDNB was significantly depressed in mice, unaltered in rats and significantly increased in guinea-pigs by Ni. The hepatic GST activity toward DCNB was significantly inhibited in mice whereas no significant alteration was observed in rats. In guinea-pigs, Ni caused significant increase in hepatic GST activity for DCNB. However, hepatic GST activity toward EAA was significantly inhibited in mice whereas significantly increased in rats and guinea-pigs. These results seem to indicate that i) there exists quantitative, but not qualitative, differences among the hepatic monooxygenases of rodents in response to Ni, mice being more sensitive than rats and guinea-pigs, ii) the influence of Ni on hepatic GSH level varies depending on the animal species and iii) the hepatic GSTs of rodents are differentially regulated by Ni.