Experimental evaluation of toxic properties of target antitumor drug aimpila

Abstract

Background. Currently, the drugs, acting directly on tumor molecular or cellular targets, are actively designed. Target antitumor drug aimpila is atractyloside alpha-fetoprotein noncovalent complex. The development of this formulation is based on the ability of alpha-fe-toprotein, as a transport protein, to deliver cytotoxic agents into the cells that have alpha-fetoprotein receptors. Objective: to investigate the toxicity of aimpila in chronic experiment on rabbits. Materials and methods. The study was performed in male and female “Soviet chinchilla” rabbits. Final drug formulation (aimpila in gelatin capsules) was administrated per os at 1 and 10 therapeutic doses (0.05 and 0.5 mg/kg respectively) for 30 days with interval of 24 h. During the study dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed in days 1 and 30 post treatment, then their internal organs were subjected to histological evaluation. Results. The study demonstrates that the treatment with aimpila for 30 days in single therapeutic dose of 0.05 mg/kg had no effect on the clinical and laboratory parameters or the morphological structure of the internal organs of rabbits. Signs of hepato-, nephro-, cardio-and gastrointestinal toxicity were found in group of rabbits, treated with high dose of drug. The structural damages in liver were clinically supported with a significant increase of aspartate aminotransferase level in serum. Pathological changes in the kidneys were accompanied by a significant increase of urobilinogen and ketone bodies levels in the urine. Signs of cardio- and gastrointestinal toxicity were documented only by microscopic pathology observation. These abnormalities were reversible within 30 days. Conclusions. Aimpila formulation displayed dose-dependent and reversible toxicity and can be recommended to further investigation.