Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo

Am J Physiol. 1997 Aug;273(2 Pt 1):G530-6. doi: 10.1152/ajpgi.1997.273.2.G530.

Abstract

Inflammatory stimulation of the liver induces nitric oxide (NO) biosynthesis and suppression of detoxication. In this study the effect of NO biosynthesis on cytochrome P-450 (CYP) enzyme activity was investigated by comparing in vivo and in vitro assays. To establish liver inflammation, CD rats were injected with Corynebacterium parvum (C. parvum) suspension. After 5 days NO biosynthesis was highly induced as indicated by increased NO2- plus NO3- serum concentrations. At the same time the aminopyrine breath test (ABT), measuring CYP activity in vivo, was reduced to 42% and the in vitro assay of aminopyrine turnover was suppressed to 12% of NaCl- injected controls. When C. parvum-injected animals were treated with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), CYP activities significantly improved with an ABT of 76% and an in vitro aminopyrine turnover of 47% of controls. Neither C. parvum injections nor L-NMMA treatment resulted in a significant change of CYP protein concentrations. These data indicate that suppression of xenobiotic metabolism can be attenuated by inhibition of NO biosynthesis during an ongoing process of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors / pharmacology
  • Gram-Positive Bacterial Infections
  • Hepatitis, Animal / metabolism*
  • Hepatitis, Animal / microbiology
  • Hepatitis, Animal / physiopathology*
  • Inactivation, Metabolic*
  • Liver / enzymology
  • Liver / pathology
  • Liver / physiopathology*
  • Male
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Osmolar Concentration
  • Propionibacterium acnes
  • Rats
  • Rats, Inbred Strains
  • omega-N-Methylarginine / pharmacology

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • omega-N-Methylarginine
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Cytochrome P-450 CYP1A2