Keywords
Abstract
The aim of the study was to investigate the association between nitric oxide (NO) synthesis and hepatoprotective effects of L-ornithine L-aspartate (LOLA) in cytolysis and cholestasis syndromes induced by toxic liver injury with carbon tetrachloride (CCl4).
The study was performed on 24 white adult male rats. Acute toxic hepatitis was induced by a single intraperitoneal injection of carbon tetrachloride at a dose 2 g/kg in the form of 50 % solution, prepared on olive oil. Corrective agents, LOLA (at a dose 200 mg/kg), and N-nitro-L-arginine methyl ester (L-NAME)
(at a dose 10 mg/kg in the form of 1 % aqueous solution), were administered intraperitoneally, once a day, for 6 days. The study was performed on day 7th. Biochemical studies were performed using standard reagent kits «Spaynlab». Histological sections of liver tissue were stained with hematoxylin and eosin. Oneway analysis of variance and Origin 7.5 (Origin Lab Corporation, USA), Statistica 10 (Stat Soft, USA) and Microsoft Excel XP (USA) were used for statistical processing of the results. The results of this study indicate that the use of L-NAME, a competitive non-selective inhibitor of NO synthesis, in rats with toxic liver injury treated with LOLA, slowed the recovery of hepatocytes in the portal tract and neutralized the ability of LOLA to prevent the increase in alanine aminotransferase and aspartate aminotransferase activity. LOLA treatment also reduced alkaline phosphatase and gamma-glutamyltransferase activity, but concomitant administration of L-NAME reversed these effects. Loss of efficacy of LOLA in the presence of L-NAME means that the drug realizes these effects through a mechanism mediated by NO synthesis. At the same time, the introduction of L-NAME did not affect LOLA’s properties to inhibit increase in liver weight, augmentation in total cholesterol and total bilirubin concentration, which indicates that these effects are exerted independently on the activity of NO synthase.
Therefore, 7 days after toxic liver injury, induced by carbon tetrachloride, LOLA prevents cytolysis and increase in alkaline phosphatase and gamma-glutamyltransferase activity through a NO-mediated pathway, however, the reduction in total bilirubin and total cholesterol is posed independently on NOS activity.