Effect of endotoxin and its degradation products on hepatic mixed-function oxidase and heme enzyme systems in mice

Effect of Salmonella minnesota R595 endotoxin (R595 GL) and its chemical degradation products on hepatic cytochrome P-450, delta-aminolevulinic acid (ALA) synthetase and heme oxygenase activity in mice was examined. The levels of cytochrome P-450 and ALA synthetase activity were significantly decreased following the administration of R595 GL, whereas heme oxygenase activity was markedly increased. The effects of endotoxin were dose-dependent for the range of about 1 to 2 micrograms per mouse. The result of a comparative study using R595 GL and its degradation products suggested that intact lipid A moiety plays an important rôle in the activity of endotoxin. In addition, it was found that the depressant effect of endotoxin on the hepatic mixed-function oxidase system in mice was abrogated by treatment with cortisone.