Avaluation of morphofunctional condition of rats organism for study of toxicity of the preparation tilmicosine basis

Abstract

The article presents the study results of the acute and subacute toxicity of the veterinary drug “Tylmozyn 25” (solution for oral administration) based on tilmicosin. Intra-gastric administration of “Tylmozyn 25” to white mice at a dose of 25000 mg/kg of body weight caused the death of 100% of the animals, a dose of 15000 mg/kg of body weight caused the death of 66% of the white mice. The average time of death was 2 and 5 hours correspondingly. While determining the toxicity of “Tylmozyn 25” in white rats, we did not spot the death of any studied animal at any administered dose (5000, 15000, 25000 mg/kg of body weight). Based on the result of our study, we conclude that the veterinary drug Tylmozyn 25 belongs to the fourth of toxicity class – low toxic substances. LD50 of Tylmozyn 25 in white mice is 14167 mg/kg, while in white rats LD50 is higher than 25000 mg/kg. Testing on white rats intra-gastric drug “Tylmozyn 25” during for 14 days, both in therapeutic (80 mg/kg of body weight) and 10-fold doses (800 mg/kg of body weight) did not cause animal death, but caused a decrease in body weight, a significant decrease in the coefficients of weight of the liver and spleen and a tendency to increase the coefficients of weight of the heart and lungs compared with the animals of the control group. Animals which got the drug at a dose of 800 mg/kg of body weight showed erythrocytosis, leukopenia, increased enzymatic activity of AST, ALT, and LDH, the content of total protein against to decrease urea and creatinine, which may indicate impaired liver, kidney function and hematopoietic organs. The macroscopic and microscopic structure of the internal organs of the experimental rats is preserved. Rats receiving a tenfold therapeutic dose of the drug for 14 days, histologically revealed the most granular protein dystrophy in the liver and kidneys, which was manifested by discomplexation of the lamellae, presence of hepatocytes with uneven granular cytoplasm, slightly colored cytoplasm, hypertrophied nuclei, renal convoluted tubules and narrowing of their lumen, compaction of the mesh of the renal corpuscle. In the myocardium, the branching, swelling of the muscle fibers, swelling of the stroma with cell infiltrates, mainly of the lympho-histiocytic series, was observed, which indicated the development of serosa myocarditis. Structural changes in the liver, kidneys and heart were confirmed by biochemical parameters of the enzymatic activity of the serum of rats of this group.