Role of nitric oxide in the inhibition of cytochrome P450 in the liver of mice infected with Chlamydia trachomatis

Oleg G. Khatsenko, Natalie S. Barteneva, Luis M. De la Maza, Yutaka Kikkawa

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 [NO(x)] 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.

Original languageEnglish
Pages (from-to)1835-1842
Number of pages8
JournalBiochemical Pharmacology
Volume55
Issue number11
DOIs
Publication statusPublished - Jun 1 1998
Externally publishedYes

Keywords

  • Chlamydia trachomatis
  • Cytochrome P450
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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