CORRECTION OF DOXORUBICIN-INDUCED HEPATOTOXICITY BY GLUCOSAMINE DERIVATIVES AND THEIR COMBINATIONS WITH QUERCETIN IN RATS
The article presents the results of the pharmacological study of glucosamine derivatives and their combinations with flavonoid quercetin as correctors of hepatotoxicity of anthracycline antibiotics, particularly doxorubicin. As the test compounds substances of glucosamine hydrochloride in conventionally therapeutic doses of 50 mg/kg, and the combination of aminosugars of glucosamine hydrochloride and N-acetylglucosamine with flavonoid quercetin in the ratio of 3:1 equivalent to glucosamine hydrochloride in a conventionally therapeutic dose of 82 mg/kg have been studied. Quercetin was used in the dose of 20.5 mg/kg as a reference medicine. To assess the degree of liver damage and severity of the hepatoprotective activity of the objects selected a number of biochemical parameters (the level of TBA-reactants of the serum and the liver homogenate, the activity of indicator enzymes of ALT, AST cytolysis, the content of the total protein, glucose, urea in the serum) have been determined; the the histomorphologic study of liver tissue has been conducted. According to the experimental results it has been found that all tested compounds have the ability to reduce the toxic effects of doxorubicin in relation to the liver. With respect to overall rating of the parameters studied a combination of aminosugars of glucosamine hydrochloride and N-acetylglucosamine with quercetin has shown the most significant hepatoprotective effect, and it can be explained by a synergistic action of its individual components directed to inhibition of free radical processes and cytolysis, inhibition of inflammation, urea formation function, protein synthesis in the liver, normalization of the carbohydrate metabolism and decrease of hypoplastic changes in the liver tissue. The results of the study experimentally substantiate the use perspectiveness of a combination of aminosugars of glucosamine hydrochloride and N-acetylglucosamine with quercetin for pharmacological correction of toxic effects of anthracycline antibiotics during anticancer therapy.