Pre-clinical stody of subchronic toxicity of ormustine in dogs

Abstract

Introduction . In N. N. Blokhin National Medical Research Center of Oncology were made preclinical toxicological studies of drmustine, a new antitumor drug from the class of nitrosoureas. The paper presents some results of study the subchronic toxicity ofdrmustine in dogs. Objective. The objective of the present study was to investigate the subchronic toxicity of о rmustine on dogs with a daily intravenous administration during 3 days. Materials and methods . The study was performed in 12 dogs of the English beagle breed of males and females. Ormustine was adminis¬tered intravenously daily during 3 days in total doses of 1, 5, 10, 20 and 30 mg/kg. During the experiment, to study the damaging effect of ormustin on organs and tissues, clinical and lab tests andpathomorphological examinations were performed. Results . Ormustin in doses of 20 and 30 mg/kg caused the death of animals on the 7th and 8th day of observation against the background of severe hemato-and gastrointestinal toxicity. In dogs receiving the drug in all doses, there were external manifestations of intoxication and changes in behavioral reactions, weight loss during the entire observation period. It was found that the drug had a dose-related myelosuppressive effect. Ormustin caused pronounced morphological changes of varying degrees of reversibility in the small intestine, kidneys, thyroid gland, liver, lymph nodes, spleen, heart and gonads; less pronounced — in the large intestine, stomach and bladder. Conclusion. According to the study, the total doses of ormustin 20 and 30 mg/kg were characterized as lethal, 5 and 10 mg/kg — high toxic, 1 mg/kg — low toxic dose.