Abstract
Background. In N.N. Blokhin Russian Cancer Research Center has been developed injectable dosage form based on the substance of indolocarbazole derivative LCS-1208, studied its antitumor activity and mechanism of antitumor effect, which was the basis for the pre-clinical study of the drug toxicity. Objective. The study of subchronic toxicity of formulation of glycoside derivative of indolocarbazole - LCS-1208 after intraperitoneal application to rats. Materials and methods. Dosage form of study drug: lyophilisate for preparation of solution for injection of 9,0 mg in vial. The study was conducted on 40 healthy non inbred male rats, which were obtained from the breeding of the N.N. Blokhin Russian Cancer Research Center. It was studied the action of the drug on the peripheral blood, the functional state of the liver, kidney and gastrointestinal tract of animals. Results. The drug LCS-1208 by daily intraperitoneal administration to rats for 15 days in the 3 studied doses (total dose 200 mg/kg, 100 mg/kg and 50 mg/kg) did not cause death of animals, had no effect on the general condition of the animals, did not cause external manifestations of toxicity, did not change behavioral responses of animals and had no effect on the functioning of the studied organs. Conclusion. The results obtained by the study of the subchronic toxicity in rats were the basis for further preclinical toxicology study of the drug LCS-1208.
Highlights
Blokhin Russian Cancer Research Center has been developed injectable dosage form based on the substance of indolocarbazole derivative LCS-1208, studied its antitumor activity and mechanism of antitumor effect, which was the basis for the pre-clinical study of the drug toxicity
The results obtained by the study of the subchronic toxicity in rats were the basis for further preclinical toxicology study of the drug LCS-1208
Изучение острой токсичности нового противоопухолевого лекарственного средства на основе производного индолокарбазола – ЛХС-1208
Summary
Изучение субхронической токсичности гликозидного производного индолокарбазола ЛХС-1208 на крысах. Блохина» Минздрава России рядом ученых была разработана инъекционная лекарственная форма на основе субстанции гликозидного производного индолокарбазола – ЛХС-1208, изучены ее противоопухолевая активность и механизм противоопухолевого действия, что явилось основанием для доклинического изучения токсичности этого препарата. Цель исследования – изучение субхронической токсичности лекарственной формы гликозидного производного индолокарбазола ЛХС-1208 при внутрибрюшинном введении крысам. Препарат ЛХС-1208 при ежедневном внутрибрюшинном введении крысам в течение 15 дней в 3 исследованных дозах (суммарные дозы 200, 100 и 50 мг/кг) не вызывал гибели животных, не оказывал влияния на их общее состояние, не вызывал внешних проявлений токсичности, не изменял поведенческие реакции животных и не оказывал влияния на функциональное состояние печени, почек и поджелудочной железы. Полученные результаты изучения субхронической токсичности на крысах явились основанием для дальнейшего доклинического токсикологического изучения лекарственного препарата ЛХС-1208. Blokhin Russian Cancer Research Center, Ministry of Health of Russia; 23 Kashirskoe shosse, Moscow, 115478, Russia
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