Determining the effect of drug "Warfarin sodium" on toxicity indicators in an acute experiment

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL
D.O. Hlavachek, O.Ye. Kondratenko
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Abstract

The drug "Warfarin sodium" refers to anticoagulants of indirect action. It contains only one substance - warfarin sodium, the toxicological indicator of which have been studied in many countries. Therefore, the range of indicators for DL50 of warfarin sodium is very large. However, warfarin sodium has not yet been studied in Ukraine, its maximum permissible concentration in the air of the work area has not been established. Significant volumes of production and use of the drug “Warfarin sodium” on the territory of Ukraine necessitate the clarification of its main toxicological indicators and the establishment of the maximum allowable concentration in the air of the working area, which includes several stages. The first of them is the purpose of this work, namely: to establish DL50 upon intragastric administration of the drug "Warfarin sodium" to two species of animals in the conditions of an acute experiment. Experimental animals (60 non-linear white rats and 70 non-linear white mice) were divided into 9 groups. Six groups were injected with the drug "Warfarin sodium" in different doses: the first group (female rats) – 58 mg/kg per animal, the second (also female rats) – 29 mg/kg, the third (male rats) – 323 mg/kg, the fourth (also male rats) – 161.5 mg/kg, the fifth (mice of both sexes) – 374 mg/kg, the sixth (also mice of both sexes) – 187 mg/kg. Three control groups (the first – 6 male rats, the second – 6 female rats, the third – 14 mice) received distilled water. As a result, the mortality rates of experimental animals were obtained, on the basis of which, using the probit analysis method, the toxicity indicator of DL50 was determined: for female rats – 15.85 mg/kg, male rats – 398.11 mg/kg and mice –645.65 mg/kg. The established DL50 for male rats after intragastric administration of the drug "Warfarin sodium" may indicate an increase in their resistance to the drug, and this determines the expediency of periodic repeated acute experiments in order to verify the relevance of previously established DL50 of sodium warfarin. According to DL50 upon intragastric administration to female rats, which are the most sensitive species of animals to it, warfarin sodium belongs to highly hazardous substances.
测定药物华法林钠对急性毒性指标的影响
药物“华法林钠”是指间接作用的抗凝血剂。它只含有一种物质——华法林钠,其毒理学指标已在许多国家进行了研究。因此华法林钠DL50的指标范围非常大。然而,在乌克兰尚未对华法林钠进行研究,工作区域空气中华法林钠的最大允许浓度尚未确定。乌克兰领土上“华法林钠”药物的大量生产和使用,需要澄清其主要毒理学指标,并确定工作区域空气中的最大允许浓度,这包括几个阶段。第一个是本工作的目的,即:在急性实验条件下,对两种动物灌胃“华法林钠”药物,建立DL50。实验动物(非线性大鼠60只,非线性小白鼠70只)分为9组。六组注射不同剂量的药物“华法林钠”:第一组(雌性大鼠)每只动物58毫克/公斤,第二组(雌性大鼠)29毫克/公斤,第三组(雄性大鼠)323毫克/公斤,第四组(雄性大鼠)161.5毫克/公斤,第五组(雌雄小鼠)374毫克/公斤,第六组(雌雄小鼠)187毫克/公斤。三个对照组(第一组- 6只雄性大鼠,第二组- 6只雌性大鼠,第三组- 14只小鼠)接受蒸馏水。得到实验动物的死亡率,在此基础上,采用概率分析法确定了DL50的毒性指标:雌性大鼠- 15.85 mg/kg,雄性大鼠- 398.11 mg/kg,小鼠- 645.65 mg/kg。雄性大鼠在给药“华法林钠”后建立的DL50可能表明其对该药物的耐药性增加,这决定了为了验证先前建立的华法林钠DL50的相关性,需要定期重复急性实验。根据对华法林钠最敏感的动物雌性大鼠灌胃的DL50,华法林钠属于高度有害物质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Medical Perspectives-Medicni Perspektivi
Medical Perspectives-Medicni Perspektivi MEDICINE, GENERAL & INTERNAL-
CiteScore
0.40
自引率
0.00%
发文量
85
审稿时长
9 weeks
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