新型喹喔啉酮(6-硝基-2(1H)-喹喔啉酮类)在Wistar大鼠体内的急性毒性评估

R. Nakache, T. Touil, A. El hessni, A. Ouichou, Y. Bahbiti, I. Berkiks, Miloud Chakit, A. Mesfioui
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引用次数: 1

摘要

摘要喹喔啉衍生物是一类重要的杂环化合物,由偶氮取代碳原子得到。喹喔啉的融合生产相对容易,因为它们显然是由苯和吡嗪这两个芳环融合合成的。我们在实验室合成了新的喹喔啉衍生物6-硝基-2(1H)-喹喔啉酮(NQX)。然而,对大鼠的相关毒性作用仍然未知。本研究旨在研究NQX对正常Wistar大鼠的急性毒性。七组雌性大鼠接受腹膜内(i.p.)注射0(对照)、20、40、60、120、200和300mg/kg的NQX,并持续14天。监测了死亡率、行为变化、体重、食物和水分摄入的变化、尿量和粪便重量。在实验结束时,处死未观察到不良反应水平(NOAEL)的大鼠,收集血液和器官,并分析血清样品中的血液学和生化参数。结果表明,NQX致死剂量50(LD50)为161.16 mg/kg。以40mg/kg的剂量(NOAEL剂量)给予NQX不会影响动物的生存能力和体重。此外,食物摄入、水分摄入和尿液排出量保持不变。此外,在NOAEL剂量下,血细胞(红细胞和白细胞)、血红蛋白、生化参数(葡萄糖、胆固醇、甘油三酯、尿素、肌酐、胆红素、总蛋白和转氨酶)和器官重量(肝、肾、脾、胰腺、心和脑)的水平没有受到影响。在正常Wistar大鼠中,在40mg/kg的剂量下NQX似乎相对节省,并且可能在初步临床试验中进行进一步分析后进行测试。
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In vivo acute toxicity assessment of a novel quinoxalinone (6-nitro-2 (1H)-quinoxalinone) in Wistar rats
Abstract The quinoxaline derivatives are an important class of heterocyclic compounds, obtained from chemical azote replacement of carbone atom. Fusion of quinoxaline production is relatively easy as they are obviously synthesized by the fusion of two aromatic rings, benzene and pyrazine. The new quinoxalinique derivative, 6-nitro-2 (1H)-quinoxalinone (NQX), has been synthesized in our laboratory. However, the related toxic effect on rat remains unknown. The present work aims to study the acute toxicity of NQX in normal Wistar rats. Seven groups of female rats received an intraperitoneal (i.p.) injection of 0 (control), 20, 40, 60, 120, 200 and 300 mg/kg of the NQX and followed for 14 days. Mortalities, behavioural changes, weight, changes in food and water uptake, urine output and weight of faeces were monitored. At the end of the experiment, the rats receiving the no-observed-adverse-effect level (NOAEL) are sacrificed, blood and organs were collected and haematological and biochemical parameters were analysed in sera sample. The results showed that the NQX Lethal Dose 50 (LD50) was 161.16 mg/kg. The administration of NQX at a dose of 40 mg/kg (NOAEL dose) did not affect animal viability and body weight. In addition, food intake, water intake and urine output remain unchanged. Furthermore, at the NOAEL dose, the levels of blood cells (erythrocytes and leukocytes), haemoglobin, biochemical parameters (glucose, cholesterol, triglycerides, urea, creatinine, bilirubin, total protein and transaminase) and organ’s weights (liver, kidney, spleen, pancreas, heart and brain) were not affected. NQX seems to be relatively saved at the dose of 40 mg/kg in normal Wistar rats and could possibly be tested after further analysis in a preliminary clinical test.
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Cogent Chemistry
Cogent Chemistry CHEMISTRY, MULTIDISCIPLINARY-
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