Effects of lipopolysaccharide (E. coli) and OK-432, a Streptococcus preparation, on the hepatic drug-metabolizing system in mice (author's transl)

Abstract

Effects of lipopolysaccharide (E. coli, LPS) and OK-432 (a Streptococcus preparation) on the activity of hepatic drug-metabolizing enzyme and on the blood concentration of aminopyrine, cyclophosphamide, or pentobarbital were studied in mice. LPS (5 mg/kg, i.v.) or OK-432 (50 KE/kg, i.v.) decreased the activity of drug-metabolizing enzymes in liver microsomes, and the greatest decrease of the enzyme activity was observed 24 h after the administration of LPS or OK-432. The levels of cytochrome P-450 and cytochrome b5 and the activities of aminopyrine N-demethylase and aniline hydroxylase in microsome decreased progressively for 24 h after the administration of LPS and then increased to the normal level within 4 days. Effect of OK-432 on the activity of these enzymes was weaker than that of LPS. The blood concentrations of aminopyrine and pentobarbital in mice treated with LPS were higher than those in untreated mice. On the other hand, the blood concentration of normustard relating to the active metabolite of cyclophosphamide was lower in mice treated with LPS. It is possible that the blood concentration of combined drugs was affected by LPS and OK-432 as a result of the depression of the hepatic drug-metabolism with a decrease in heme protein content and with an inhibition of electron transport system in liver microsomes.