STUDY OF SOME ACUTE TOXICITY INDICATORS OF MELPHALAN IN RATS
Introduction. Bone marrow suppression and gastro-intestinal toxicity are the main limiting factors for treatment of oncological patients and may cause its delaying and disruption. So, search of new effective drugs, biomaterials and substances to ameliorate side effects of anticancer chemotherapy remains actual problem. To study their protective capacity and for preclinical study we require the relevant animal model. It is known that alkylating agents possess the most toxic effect on bone marrow and mucus membranes of intestine and have radiomimetic properties.
The aim of the study – screening studies to define the main parameters of acute toxicity of melphalan in rats for further use as an animal model of cytostatic myelodepression for preclinical studies.
Research Methods. Experiments were performed on inbred rats, which were randomized into 4 groups. Melphalan at the dose of 3, 6, 9 and 12 mg/kg was injected one time intravenously into the tail vein. The main acute toxicity indicators, namely median lethal dose LD50, 1/ LD50 – absolute toxicity, LD84/ LD16 – zone of acute toxic effects, 1/( LD50–S) – the total indicator of toxicity and S – function of the inclination angle (lethal doses variability), were measured by Finney method and method offered by V. V. Prozorovskyi using software StatPlus 2009 Professional 5.8.4.
Results and Discussion. According to the regression analysis by Finney method LD50 is (4.22±0.62) mg/kg (lower limit LD50 – 3.10 mg/kg, higher limit – 5.49 mg/kg). Indicator of LD50 is (4.765±1.003) mg/kg (from 2.63 to 6.90 mg/kg) according to the method proposed by Prozorovskyi in single intravenous injection.
Conclusions. The dose of 3 mg/kg of melphalan was as a single intravenous injection was chosen for further experiments and as a model of cytostatic myelodepression for preclinical studies.
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