Toxicological profile of aimpila drug in chronic experiment on rats

Abstract

Introduction. As a rule, pharmacotherapy of neoplastic diseases is associated with side effects varying degrees of severity. This is determined by the insufficient selective action of antitumor agents and, as a result, high nonspecific toxicity. One way to solve this problem is the development of the targeted drugs, delivered the active agent to the tumor cells. Over the past decades many experimental and clinical studies were undertake, but only few of them have demonstrated clinical efficacy of targeted drugs. This determines the necessity of further search in this direction. Objective: to investigate the toxicity of aimpila, its correlation with dose and reversibility. Materials and methods. Toxicological study of aimpila, developed by Pharmaceutical Scientific Center “PharmAccess” Ltd. (Moscow), was performed in male and female outbred rats. Aimpila is atractyloside alpha-fetoprotein noncovalent complex. Capsule mass of the drug in starch gel was administrated per os at the 1 and 10 therapeutic dose (30 x 0.1 mg/kg or 30 x 1 mg/kg with 24-h interval). Dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. 5 animals in each group were sacrificed 1 and 30 days post treatment. Results. The results of the study demonstrate that the treatment with aimpila does not produce any changes in examined clinical-labora- tory parameters. Liver, renal, cardio, pancreatic and gastrointestinal toxicity of aimpila have been documented by microscopic pathology observation only in groups of rats, treated with high dose of drug. Histopathological findings of hepatotoxicity were supported by the results of clinical chemistry. Marked elevation of aspartate aminotransferase in serum was found after high dose aimpila treatment. These abnormalities were reversible during a month. Conclusion. The overall result of this study suggests the aimpila formulation has favorable toxicological profiles. Dose dependence and reversibility of toxic effects allows us to recommend it to further advance.