Og. Khatsenko et al., ROLE OF NITRIC-OXIDE IN THE INHIBITION OF CYTOCHROME-P450 IN THE LIVER OF MICE INFECTED WITH CHLAMYDIA-TRACHOMATIS, Biochemical pharmacology, 55(11), 1998, pp. 1835-1842
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.