Effect of lipopolysaccharide (from Escherichia coli) on the hepatic drug-metabolizing activities in successively LPS-treated mice.

Abstract

The effect of an acute or a successive administration of endotoxin (lipopolysaccharide obtained from Escherichia coli, LPS) on the hepatic drug-metabolizing system in vivo and in vitro was examined in mice. An acute LPS (5 mg/kg, i.v.) administration or a successive LPS (5-20 mg/kg, i.p., a day for 6 days) administration prolonged the duration of pentobarbital sleeping time and reduced the rate of hepatic microsomal metabolism of pentobarbital, aminopyrine, aniline and cyclophosphamide and reduced cytochrome P-450 content as compared with those in the control mice. No change of these parameters, however, was observed by an acute treatment with LPS to the successively LPS-treated mice. In addition, the LD50's of aminopyrine and pentobarbital and the ED50 of aminopyrine were reduced by an acute administration of LPS in control mice. No change of both parameters, however, was observed in the successively LPS-treated mice with or without an acute administration of LPS.