The aim was to establish the morphofunctional changes of liver in the experimental cirrhosis. Materials and methods: The research was conducted on 24 white male Wistar rats. Experimental cirrhosis of the liver was simulated by oral administration of CCl4 2 g/kg 2 times weekly for three months. From the selected fragments of the liver, histological specimens were done according to the conventional method and examined by light microscopy. The activity of the enzymes of cytolysis and cholestasis (ALT, AST, alkaline phosphatase), the content of components of bile (cholesterol, bilirubin and bile acids) were determined in the serum. In the blood and liver were determined the content of the final products of metabolism of nitric oxide: NO2 - and NO3 -; in the blood – the content of ceruloplasmin, lactate, pyruvate, middle molecular-weight protein MWP1 and MWP2. In the liver – the activity of succinate dehydrogenase (SDG) and cytochrome oxidase (CHO), N-demethylase and p-hydroxylase microsomal activity. The state of the system of prooxidants-antioxidants was judged by the content in the liver of thiobarbituric acid reactive substance (TBARS), lipid hydroperoxide (LHP), concentration of sulfhydril group (GSH), catalase activities (CAT), superoxide dismutase (SOD). The content of endothelial (eNOS) and inducible (iNOS) NO synthases, the concentration of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were determined by the enzyme immunoassay. Results: Cirrhosis of the liver, which is morphologically confirmed by the presence of prominent sclerosis in the periportal zones and the formation of umbel, is accompanied by the development of cytolysis and cholestasis processes with an increase in the content of components of bile in the blood (cholesterol, bilirubin and bile acids). An increase in the content of lipoperoxidation products and disturbance of the state of the enzymatic and non-enzymatic units of the antioxidant system, decrease in the activity of mitochondrial (succinate dehydrogenase and cytochrome oxidase) enzymes have been established. The activity of the detoxification processes decreases, namely the inhibition of N-demethylase and p-hydroxylase activity of the liver microsomes, so the manifestations of endotoxicosis increase. This is accompanied with decreased content of endothelial and an increased content inducible NO synthase, a concentration of a stable metabolite of nitric oxide nitrite anion in the blood increase and a decrease in the liver. Сonclusions: Experimental CCl4 cirrhosis is characterized morphologically by sclerosis in the periportal zones and the formation of umbao. The metabolic and functional cirrhoticliver is characterized by cytolysis and cholestasis activation, inhibition of detoxication, prooxidant-antooxidant, including nitrooxidative, disbalance.
This study was aimed to investigate nitric oxide-dependent mechanisms of L-ornithine-L-aspartate (LOLA) action in acute toxic liver injury in rats. Acute hepatitis was induced in Wistar rats using 50% oil solution of tetrachloromethane (CCl4) intragastrically (2 g/kg) twice in a 24 hour interval. Intraperitoneal treatment with LOLA (200 mg/kg) was started 6 hours after the second CCl4 administration and maintained for 3 consecutive days. L-Nω-Nitroarginine Methyl Ester (L-NAME) was used intraperitoneally (10 mg/kg). In CCl4-induced hepatitis, LOLA restores the structure of hepatocytes and prevents aminotransferases, alkaline phosphatase and gamma-glutamyl transferase elevation. It decreases total bilirubin concentration but does not affect increased cholesterol level. LOLA augments urea concentration, total protein level in blood and liver as well as serum and liver content of nitrite anions. LOLA enhances activity of catalase, glutathione S-transferase, manganese superoxide dismutase, increases reduced glutathione level and total antioxidant capacity and decreases thiobarbituric acid reactive substances level. The concomitant use of L-NAME inhibits the action of LOLA to enhance nitrite anions synthesis both in serum and liver, to delay the recovery of hepatocytes, to counteract LOLA effect against blood total protein reduction, to prevent the decline in aminotransferases, alkaline phosphatase,, gamma-glutamyl transferase and glutathione S-transferase activity and to reduce catalase activity and reduced glutathione level. Therefore, in CCl4-induced hepatitis, LOLA effectively prevents cytolysis and cholestasis, improves liver metabolism and protects against oxidative stress. Partially, these changes occur in nitric oxide-mediated mechanism since the use of L-NAME declines most of LOLA effects.
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