Endotoxin depression of hepatic mixed function oxidase system in C3H/HeJ and C3H/HeN mice

Abstract

The effect of endotoxin to depress the hepatic drug-metabolizing enzyme activity has been studied in the C3H/HeJ and C3H/HeN strains of mice. The C3H/HeJ mouse strain is generally considered to be unresponsive to the biological effects of endotoxin. However, injection of these mice with 0.5 mg/kg body weight of E. coli endotoxin (Westphal extracted) produced a decrease in the rate of N-demethylation of ethylmorphine and in the levels of cytochrome P-450 and cytochrome b5 comparable to that observed in the endotoxin-sensitive C3H/HeN mouse strain. Although the mechanism of endotoxin action to decrease hepatic microsomal drug-metabolizing activity is presently unknown, the results suggest that: 1) the C3H/HeJ mouse strain is responsive to this endotoxin effect, and 2) that cellular constituents other than B-cells or macrophages are probably involved in eliciting the response, since these cells of the C3H/HeJ mouse are unresponsive to endotoxin.