Acute and subacute toxicity of the drug based on tylosin tartrate

Abstract


 The article presents the results of a study of the acute and subacute toxicity of the drug TILOTAR (a water-soluble powder for oral administration) made on the basis of tilmicosin. As a result of the research it was found that the drug “TILOTAR” refers to the 4th class of toxicity, that is, to low-toxic substances. After intragastric administration of the drug to white mice and rats at doses of 2500, 5000, 7500 mg/kg, all animals remained alive. Short-term inhibition was recorded in laboratory animals, which were given the drug at the maximum dose. Further changes in the clinical state of the animals of the experimental groups were not observed. The study of subacute toxicity of the drug “TILOTAR” showed that 14-day administration of a therapeutic dose of the drug leads to a decrease in erythropoiesis, the appearance of old forms of erythrocytes, damage to hepatocytes, the appearance of eosinophils, γ-globulins, a decrease in protein biosynthesis, increased kidney function. The introduction of a 10-fold dose within 14 days reduced the body weight of the rats, leading to abnormalities in the liver and kidneys, and a decrease in the mass of the spleen. An increase in urea blood concentration and a decrease in creatinine may indicate impaired renal function in animals that were given a tenfold dose of the drug, and an increase in the level of α- and γ-globulins against the background of a decrease in body weight of rats indicates an overload of the body’s immune system. In rats of the therapeutic group, homeostasis was maintained by enhancing kidney function, accompanied by a decrease in the number of erythrocytes due to young forms and the appearance of mature erythrocytes with a high level of hemoglobin (MCH), some destruction of hepatocytes (high level of alkaline phosphatase activity) while reducing the amount of albumin, an increase in relative levels of α- and γ-globulins. In the conducted experiments it was established that the macroscopic and microscopic structure of the internal organs of rats, while studying the subacute toxicity of the drug “TILOTAR”, was preserved, no macroscopic changes were revealed. In rats receiving a 10-fold therapeutic dose of the drug for 14 days, focal protein dystrophy of the liver and kidneys was histologically established.