AJP - Gastrointestinal and Liver Physiology, Vol 273, Issue 2 530-G536, Copyright © 1997 by American Physiological Society
Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo
A. Veihelmann, T. Brill, M. Blobner, I. Scheller, B. Mayer, M. Prolls, S. Himpel and J. Stadler
Department of Surgery, Technische Universitat Munchen, Germany.
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.
