Role of nitric oxide in the inhibition of cytochrome P450 in the liver of mice infected with Chlamydia trachomatis.
Biochem Pharmacol
; 55(11): 1835-42, 1998 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-9714302
ABSTRACT
In this study, we attempted to determine the effect of a systemic infection with Chlamydia trachomatis on cytochrome P450(CYP)-dependent metabolism in mice. Furthermore, we wanted to assess if these effects were mediated through NO. BALB/c(H-2d) female mice were inoculated intraperitoneally with the C. trachomatis mouse pneumonitis (MoPn) biovar, and induction of NO synthase (NOS) was detected by measuring [NOx] levels and inducible NOS protein content in peritoneal macrophages by Western 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 was a significant increase in the intensity and the length of the infection. 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 suggest that C. trachomatis infection can depress cytochrome P450 in a manner similar to other types of infections and that NO is likely to be a mediator of this depression. This finding may be of significance to patients taking drugs that are metabolized by phase I enzymes during infections with some bacteria such as C. trachomatis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chlamydia Infections
/
Chlamydia trachomatis
/
Cytochrome P-450 Enzyme System
/
Isoenzymes
/
Liver
/
Nitric Oxide
Limits:
Animals
Language:
En
Journal:
Biochem Pharmacol
Year:
1998
Document type:
Article
Affiliation country:
United States
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM