title: Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo.
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.
authors.affiliation: Department of Surgery, Technische Universität München, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Veihelmann
authors.forename: T
authors.initials: T
authors.lastname: Brill
authors.forename: M
authors.initials: M
authors.lastname: Blobner
authors.forename: I
authors.initials: I
authors.lastname: Scheller
authors.forename: B
authors.initials: B
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: Prölls
authors.forename: S
authors.initials: S
authors.lastname: Himpel
authors.forename: J
authors.initials: J
authors.lastname: Stadler
mesh_terms: D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections; D006520:Hepatitis, Animal / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology*; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009994:Osmolar Concentration; D011425:Propionibacterium acnes; D051381:Rats; D011919:Rats, Inbred Strains; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019388:Cytochrome P-450 CYP1A2