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Objective. The aim of the study was to research the toxicity of L-asparaginase Was79 in rabbits. Materials and methods. Chronic toxicity of L-asparaginase Was79, obtained by modification of native enzyme Wolinella succinogenes in Research Institute of Genetics and Selection, was performed in male and female Russian chinchilla rabbits. L-asparaginase was injected intravenously at the 1 and 5 therapeutic dose (15 x 100 IU/kg or 15 x 500 IU/kg with 24-h interval). The following parameters were tested: body mass, clinical and biochemical blood tests, urinalysis, electrocardiography, pathomorphological evaluation of internal organs. Resutls. The results of the study suggest that the treatment with L-asparaginase Was79 does not influence on the function of heart and kidneys, but damages their structure. Loss in body mass, diarrhea and alteration of stomach and intestine mucosa could be interpreted as evidence of gastrointestinal toxicity. Hematological toxicity was exhibited as a decrease of total leukocyte count, lymphocyte and neutrophils count level in peripheral blood and atrophy of lymphoid tissue of the spleen, thymus and lymph nodes. Elevation of total and direct bilirubin in serum and histopathological findings in liver were found in groups treated with both high and low doses of Was79. Conclusion. Most of these abnormalities were reversible and dose-dependent.

Исследована противоопухолевая активность и проведено доклиническое токсикологическое изучение фармацевтической композиции ЛХТА-1975, содержащей в качестве основного действующего компонента хлорид трис (1-пентил-ІН-индол-3-ил) метилия. Достоверный ростингибирующий эффект показан на мышах с лимфолейкозом Р-388, аденокарциномой молочной железы АК-755 и меланомой В-16. По данным токсикологических исследований препарат имеет значительный интервал между лечебными и токсическими дозами, что потенциально делает его интересным для дальнейшего изучения. При применении в дозах, в 5-10 раз превышающих терапевтические, композиция не вызывала токсических изменений в органах и тканях.

Toxicological study of L-asparaginase Was79, obtained by modification of native enzyme Wolinella succinogenes in Research Institute of Genetics and Selection, was performed in male and female inbred rats. L-asparaginase was injected intraperitoneally at the 1 and 10 therapeutic dose (15x1200 IU/kg or 15x12000 IU/kg with 24-h interval). 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 15 days post treatment. At necropsy, the organs were inspected macroscopically. The mass coefficients of heart, kidneys, liver, spleen and thymus were calculated. The pathomorphological evaluation was performed for internal organs. The results of the study demonstrate that the treatment with L-asparaginase Was79 did not produce any changes in body weight, hematology, blood biochemical or urinary parameters. Hematological, renal, gastrointestinal, and pancreatic toxicity of L-asparaginase have been documented only by microscopic pathology observation. Liver toxicity, revealed in the histopathological findings, was supported by the results of clinical chemistry. Marked elevation of ALT and alkaline phosphatase in serum was found in both treated groups. Most of these abnormalities were reversible and dose-dependent.