Keywords
Abstract
The purpose of the work is to investigate the levels of hydroxyproline in the liver and kidneys and to evaluate their relationship with the serum content of TGF-β and IGF-1 in chronic toxic hepatitis (induced by tetrachloromethane and ethanol) and correction with lisinopril and L-arginine L-glutamate (comparison drug). The investigation were performed on 48 white non-linear female rats aged 1,5 months with a body weight of 60–80 g. The animals were divided into four groups: group 1 – intact rats; group 2 – animals with chronic toxic hepatitis, which was modeled by intragastric administration of a 20 % oil solution of tetrachloromethane at a dose of 0,1 ml/100 g of weight twice a week in combination with a 5 % ethanol solution for 8 weeks; group 3 – animals with chronic toxic hepatitis, which were treated with lisinopril (20 mg/kg/day, intragastric) for 8 weeks; group 4 – animals with chronic toxic hepatitis, which received treatment with the comparison drug L-arginine L-glutamate (35 mg/kg/day, intragastric). The content of transforming growth factor beta (TGF-b) and insulin-like growth factor 1 (IGF-1) was determined in blood serum by immunoenzymatic methods. The content of free hydroxyproline in postnuclear supernatants of liver and kidney homogenates was determined by reaction with para-dimethylaminobenzaldehyde. Chronic toxic hepatitis was accompanied by collagen metabolism disorders and the development of liver and kidney fibrosis, which was evidenced by an increase in the content of free hydroxyproline by 52,7 and 39,2 % (p < 0,05) respectively in the liver and kidneys of rats compared to the indicators of the control group. At the same time, a probable increase in content of TGF-b and IGF-1 in blood serum was recorded by 13,5 and 13,7 %, respectively, compared to the control. Under these conditions, the levels of TGF-b and IGF-1 in blood serum were correlated with the content of free hydroxyproline in the liver and kidneys (r = 0,62–0,82, p < 0,05). The use of lisinopril in chronic toxic hepatitis showed antifibrogenic effect in the liver and kidneys (the content of free hydroxyproline in the liver and kidneys was 23,2 and 24,7 % lower, compared to untreated animals, p < 0,05), which exceeded that in the drug L-arginine L-glutamate comparison. The antifibrogenic effect of lisinopril was associated with a significant decrease in serum levels of TGF-b and IGF-1 by 54,1 and 12,1 %, (p < 0,05) respectively, compared to untreated animals (r = 0,58–0,78, p < 0,05). The data obtained allow to recommend the use of lisinopril for prevention fibrosis of the liver and kidneys in chronic toxic hepatitis.