Experimental evaluation of toxic properties of LCTA-2034 by the oral route of administration
Introduction. New antitumor multitarget drug LCTA-2034, obtained in Gause Institute of New Antibiotics, has demonstrated high activity against prognostically significant transplantable mice tumors by the oral application. Objective. To investigate the toxicological properties of LCTA-2034 by the oral route of administration on rats. Materials and methods. Toxicological study of LCTA-2034 was performed on 30 male Wistar rats. Drug substance dissolved in potable water. 2 % solution was administrated per os at the 1 and 5 therapeutic dose (15 х 20 mg/kg or 15 х 100 mg/kg with 24-h interval). 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 1 and 30 days post treatment. The internal organs were subjected to histological evaluation. Results. The results of the study demonstrate that the treatment with low dose of LCTA-2034 does not produce any changes in majority of examined clinical-laboratory parameters with the exception of urinalysis revealed hematuria on day 1 post treatment. Microscopic pathology observation showed structure abnormalities of varying severity in liver, kidneys, heart, stomach, jejunum, ileum, spleen and thymus. Administration of high dose of LCTA-2034 caused mortality of 2 rats in group. The rest of the rats were observed a body weight lag, decrease of total leukocyte and erythrocyte count, hemoglobin and hematocrit level, relative weight of the thymus. Erythrocytes and nitrates were found in urine both on day 1 and on day 30 post treatment. In groups treated with high dose of the drug in addition to the listed above organs damage of the structure of lymph nodes, pancreas, ileum and brain was detected. Conclusion. Revealed toxic properties of LCTA-2034 depended on dose. Multiple administration of 1 therapeutic dose of the drug produces transient toxic effects completely reversible within 30 days.