Experimental study of the hepatoprotective effect of the 2.6-dimethyl-n-pyridine-oxide complex with succinic acid (Poteitin) on the model of toxic hepatitis caused by tetrachloromethane

Abstract

Plant growth regulators (PGR), in particular, methyl derivatives of pyridine N-oxide, reduce the acute toxicity of pesticides, reduce the hepatotoxic effects of chlorpyrifos and ease the course of intoxication under long-term exposure. The role of the body’s defence systems under the combined effects of PGR and pesticides has not yet been sufficiently elucidated. The study of the protective effect of PGR Poteitin under the conditions of toxic damage to the liver by carbon tetrachloride (CCl4) will allow finding out the mechanisms of its combined action. The results of the research will be used to develop preventive measures for pesticide poisoning. Aim. Investigate the hepatoprotective properties of the 2.6-dimethylpyridine N-oxide complex with succinic acid (Poteitin) on the model of acute hepatitis caused by carbon tetrachloride. Materials and Methods. Acute hepatitis was modelled on male Wistar Han rats with subcutaneous injection of CCl4 (pure substance) in petroleum jelly oil (0.8 ml/100 g of body weight) for 2 days. Poteitin was administered at the doses of 23 and 0.23 mg/kg, reference substance Silybor 35 – at the dose of 5 mg/kg. Intact rats received petroleum jelly oil in the same volumes. Poteitin and Silybor were administered in a treatment-prophylactically regimen, orally 1 hour pre- and 2 hours post-CCl4. The activity of enzymes of cytolysis and cholestasis, indicators reflecting liver function, the content of lipid peroxidation (LP) products and antioxidant activity were determined in blood serum. Histological studies of liver tissue were carried out. The index of effectiveness of the protective effect of Poteitin was calculated The results were statistically processed using the one-way ANOVA followed by Fisher's LSD post-hoc test. Results and Discussion. CCl4 caused acute liver damage: increased activity of markers of cytolysis and cholestasis, decrease in a number of functional tests, activity of catalase, LP products accumulation, fatty and balloon dystrophy of hepatocytes, lympho-leukocyte infiltration. Poteitin on the background of CCl4 contributed to the normalization of the activity of markers of cytolysis and cholestasis, the restoration of functional indicators, reduced the content of LP products, increased the activity of catalase, and reduced liver damage. The protective effect of Poteitin was not inferior to Silybor. Conclusions. 1. Under the conditions of acute hepatitis, carbon tetrachloride causes moderate liver damage. 2. Poteitin at the doses of 23 and 0.23 mg/kg has a pronounced hepatoprotective effect: it normalizes the activity of enzymes of cytolysis and cholestasis, functional indicators – the level of glucose, cholesterol, total protein and bilirubin, urea; reduces the intensity of LP and activation of the antioxidant system. 3. The protective effect of Poteitin at both tested doses as cytolysis and cholestasis indicators, functional tests and morphostructural changes in the liver is comparable to the reference drug Silybor. The protective effect of Poteitin, determined by the intensity of LP, is greater than that of Silybor. Keywords: acute hepatitis, carbon tetrachloride, hepatoprotective effect, 2.6-dimethylpyridine N-oxide complex with succinic acid.