Cytochrome P-450 mediated metabolism in active murine systemic lupus erythematosus

In a comparison of NZB/NZW female mice either with active systemic lupus erythematosus (SLE) (28-33 weeks of age) or without overt SLE (7-13 weeks), the hepatic microsomal activities of ethoxycoumarin O-deethylation and aminopyrine N-demethylation were decreased 32% (p less than 0.05) and 28% (p less than 0.03), respectively, and cytochrome P-450 levels were decreased 34% (p less than 0.01) in the mice with active SLE. These changes were not associated with age differences alone in 2 nonautoimmune strains. Active murine SLE is thus associated with significant depressions in both hepatic cytochrome P-450 levels and microsomal enzyme activities. The metabolism of drugs and endogenous substrates may thus be impaired in active SLE.