Experimental assessment of the toxicity of a cardiac drug based on a phosphodiesterase-3 inhibitor and ethylmethylhydroxypyridine succinate

Abstract

The study aimed to establish the parameters of chronic toxicity of the newly developed drug based on phosphodiesterase-3 inhibitor and ethylmethylhydroxypyridine succinate in experiments on laboratory animals. The analysis was performed on white sexually mature young male Wistar rats weighing 170–185 g. Four groups of white rats were formed. The first experimental group was administered Bendamine based on a phosphodiesterase-3 inhibitor and ethylmethylhydroxypyridine succinate at a therapeutic dose. Rats of the second experimental group were injected with the experimental drug in a 5-fold dose. Rats of the third experimental group were administered the drug in a 10-fold dose. The fourth group served as control. The study of chronic toxicity of Bendamine in white rats indicates that long-term 30-day administration in therapeutic doses or 5-fold dose does not cause clinical signs of poisoning, as evidenced by the physiological limits of fluctuations in the studied morphological and biochemical parameters of blood rats. Prolonged administration of Bendamine to rats in a 10-fold dose is accompanied by a slight suppression of the body's physiological state, as indicated by a decrease in total erythrocytes and hemoglobin by 10.1 % against an increase in white blood cells by 59.8% (P < 0.001). In addition, there was a decrease in the functional state of the liver, as evidenced by a probable reduction in total protein by 8.0% and urea – by 13.5 %, as well as an increase in ALT, AST, and alkaline phosphatase by 31.6 %, 7.4 %, and 53.9% respectively. Probable changes in the coefficients of liver and spleen mass have been established. When administered intramuscularly to rats with the drug Bendamine for 30 days, the macroscopic and microscopic structure of the studied internal organs is preserved in all groups of animals. The second experimental group revealed reversible moderate histostructural changes in the liver and kidneys. In rats treated with ten times the therapeutic dose of the drug, histologically found hemodynamic disorders and alterations in dystrophic nature, mainly of protein origin, with focal localization in the parenchyma of the liver, kidneys, and myocardium, which in most cases are reversible and result from the compensatory response. Macroorganism on the introduction of a high dose of the study drug.