Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo
Autor: | T. Brill, B. Mayer, Manfred Blobner, M. Prolls, S. Himpel, I. Scheller, A. Veihelmann, J. Stadler |
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Rok vydání: | 1997 |
Předmět: |
Male
medicine.medical_specialty Physiology Biology Hepatitis Animal Nitric Oxide Nitric oxide chemistry.chemical_compound In vivo Cytochrome P-450 CYP1A2 Physiology (medical) Internal medicine medicine Animals Cytochrome P-450 Enzyme Inhibitors Propionibacterium acnes Enzyme Inhibitors Gram-Positive Bacterial Infections omega-N-Methylarginine Hepatology Osmolar Concentration Gastroenterology Cytochrome P450 Rats Inbred Strains In vitro Enzyme assay Rats Nitric oxide synthase Endocrinology chemistry Liver Enzyme inhibitor Inactivation Metabolic biology.protein Nitric Oxide Synthase Drug metabolism |
Zdroj: | ResearcherID |
ISSN: | 0002-9513 |
Popis: | 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. |
Databáze: | OpenAIRE |
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