ROLE OF NITRIC-OXIDE IN THE INHIBITION OF CYTOCHROME-P450 IN THE LIVER OF MICE INFECTED WITH CHLAMYDIA-TRACHOMATIS

In this study, we attempted to determine the effect of a systemic infe ction with Chlamydia trachomatis on cytochrome P450(CYP)-dependent met abolism in mice. Furthermore, we wanted to assess if these effects wer e mediated through NO. BALB/c(H-2d) female mice were inoculated intrap eritoneally with the C. trachomatis mouse pneumonitis (MoPn) biovar, a nd induction of NO synthase [NOx] was detected by measuring [NO,] leve ls and inducible NOS protein content in peritoneal macrophages by West ern blotting. Recovery of C. trachomatis from liver, lung, and spleen peaked at 4 days postinfection. Following cotreatment with N-G-nitro-L arginine methyl ester (L-NAME), an inhibitor of NO synthase, there wa s a significant increase in the intensity and the length of the infect ion. Six days after inoculation with C. trachomatis, CYP1A- and CYP2B- mediated metabolism in the liver of the mice was diminished up to 49% of control levels. However, when animals were treated with N-G-nitro-L -arginine methyl ester at days 4 and 6 postinfection, the decrease in the metabolism of CYP1A and CYP2B was largely blocked. These results s uggest that C. trachomatis infection can depress cytochrome P450 in a manner similar to other types of infections and that NO is likely to b e a mediator of this depression. This finding may be of significance t o patients taking drugs that are metabolized by phase I enzymes during infections with some bacteria such as C. trachomatis. (C) 1998 Elsevi er Science Inc.