Preclinical Study of Subchronic Toxicity of the Drug on the Basis of Acadesine in Rats

Abstract

Introduction At the national medical research center of оncology N.N. Blokhin preclinical toxicological studies of a lyophilized dosage form of a drug based on acadesin, a new antitumor drug, were conducted. The aim of the study to study the subchronic toxicity of the drug on the basis of acadesine in rats to evaluate its toxicity. Materials and methods The study was conducted on 40 noninbred male mongrel rats. The drug was administered intraperitoneal daily 15-fold in total doses of 750, 1150 and 2300 mg/kg. Clinical and laboratory tests were performed during the entire observation period (30 days). The pathomorphological study was performed on the 1st and 30 th day of observation. Results It was found that the drug based on acadesin, when applied repeatedly to rats in all the studied doses, did not cause changes in the indicators of peripheral blood of animals, morphological changes in all the studied organs and tissues of animals (except the kidneys), functional changes in the state of the liver, heart, kidneys and gastrointestinal tract. However, morphologically revealed changes in the kidneys when using the drug in the total dose of 1150 mg/kg on the 1st and 30 th day of observation, and in the total dose of 2300 mg/kg only on the 30 th day of observation. Conclusion The detected toxic effect of the drug based on acadesin on the kidneys of rats is dose-dependent. When using the drug in the course of the course at a total dose of 750 mg/kg, which is 60 times higher than the single therapeutic dose for rats (12.5 mg/kg), toxic manifestations were completely absent during the entire period of observation. This allowed us to recommend a drug based on acadesin for further research.