Inhibition of nitric oxide production increases dimethylnitrosamine-induced liver injury in rats
| Autor: | Hajime Nawata, Shoji Nagase, Hironori Sakai, Kusuo Ayukawa, Hidehiko Isobe |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Arginine Pharmacology Nitric Oxide Nitroarginine Dimethylnitrosamine Nitric oxide chemistry.chemical_compound medicine Animals Platelet Enzyme Inhibitors Rats Wistar Liver injury Prothrombin time Hepatology biology medicine.diagnostic_test Chemistry Microcirculation medicine.disease Rats Nitric oxide synthase NG-Nitroarginine Methyl Ester Coagulation Biochemistry biology.protein Chemical and Drug Induced Liver Injury Nitric Oxide Synthase |
| Zdroj: | Journal of Hepatology. 23:601-604 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/0168-8278(95)80068-9 |
| Popis: | Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effect of blocking the production of NO in a dimethylnitrosamine-induced liver injury model. Wistar male rats received dimethylnitrosamine (50 micrograms/kg) intraperitoneally, and were treated with N omega-nitro-L-arginine, an inhibitor of nitric oxide synthase, or N omega-nitro-D-arginine, an inactive isomer. Each arginine derivative (40 mg/kg) was injected intraperitoneally every 6 h. Twenty-four hours after dimethyl-nitrosamine administration, we observed a significant increase in the serum level of alanine aminotransferase in the N omega-nitro-L-arginine group compared with the N omega-nitro-D-arginine group. The N omega-nitro-L-arginine-treated group also exhibited a significant reduction in platelet count, a prolongation of prothrombin time, and an elevation of plasma soluble fibrin monomer complex levels. Sinusoidal congestion, intravascular coagulation, and coagulation necrosis around the central veins were prominent in the N omega-nitro-L-arginine group. In conclusion, the inhibition of nitric oxide production exacerbated the hepatic damage induced by dimethylnitrosamine, mediated by the acceleration of intravascular coagulation. |
| Databáze: | OpenAIRE |
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