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姜黄素微乳剂的犬急性和亚慢性毒性及遗传毒性。

Acute and subchronic toxicities in dogs and genotoxicity of honokiol microemulsion.

机构信息

Department of Radiological and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China; Shanxi Key Laboratory of Drug Toxicology and Drug for Radiation Injury, Taiyuan 030006, China.

Department of Radiological and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China; Shanxi Key Laboratory of Drug Toxicology and Drug for Radiation Injury, Taiyuan 030006, China.

出版信息

Regul Toxicol Pharmacol. 2018 Jun;95:362-370. doi: 10.1016/j.yrtph.2018.04.010. Epub 2018 Apr 12.

Abstract

This article aims to conduct toxicity test research on honokiol microemulsion(HM) to provide reference frame for the safe dose design as well as the toxic and adverse reaction monitoring in clinic. High performance liquid chromatography (HPLC) method was adopted to determine the concentration, stability and uniformity of HM and the results indicated that the test sample was conformed to the toxicity test requirements. In the acute toxicity test, six intravenous drip dosages, namely, 100.0, 66.7, 44.4, 19.8, 8.8, and 3.9 mg/kg were set, with one beagle dog in each dosage, respectively. In addition, the results also demonstrated that the approximate lethal dose range of HM was 66.7-100.0 mg/kg. In the subchronic toxicity test, beagle dogs were intravenously dripped with HM at doses of 1.25, 0.25 and 0.05 mg/kg for 30 days. During the test period, signs of gross toxicity, behavioral changes, body weight, rectal temperature, food consumption, ophthalmoscopy, electrocardiography, urinalysis, blood biochemistry, coagulation, hematology, organ weights and histopathology were examined. Under the present study conditions, the no-observed-adverse-effect level for HM was estimated to be 0.25 mg/kg. According to the results of bacterial reverse mutation, chromosomal aberration and micronucleus assays, HM exhibited no notable genotoxicity both in vivo and in vitro.

摘要

本文旨在对厚朴酚微乳(HM)进行毒性试验研究,为临床安全剂量设计及毒副反应监测提供参考依据。采用高效液相色谱(HPLC)法测定 HM 的浓度、稳定性和均匀性,结果表明试验样品符合毒性试验要求。在急性毒性试验中,分别设置了 6 个静脉滴注剂量,即 100.0、66.7、44.4、19.8、8.8 和 3.9mg/kg,每个剂量各有 1 只比格犬。此外,结果还表明 HM 的近似致死剂量范围为 66.7-100.0mg/kg。在亚慢性毒性试验中,比格犬分别以 1.25、0.25 和 0.05mg/kg 的剂量静脉滴注 HM,连续 30 天。在试验期间,观察了大体毒性、行为变化、体重、直肠温度、食物消耗、眼科学、心电图、尿液分析、血液生化学、凝血、血液学、器官重量和组织病理学的变化。在本研究条件下,HM 的无观察不良效应水平估计为 0.25mg/kg。根据细菌回复突变、染色体畸变和微核试验的结果,HM 在体内和体外均无明显的遗传毒性。

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