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Short-term toxicity study of 1-aminobenzotraizole, a CYP inhibitor, in Wistar rats
Drug and Chemical Toxicology ( IF 2.6 ) Pub Date : 2020-11-29 , DOI: 10.1080/01480545.2020.1850755
Santosh Kumar Pandey 1 , Harish Nakka 1 , Sudhakar R Ambhore 1 , Shalini Londhe 1 , Vinod Kumar Goyal 1 , Ramakrishna Nirogi 1
Affiliation  

Abstract

1-Aminobenzotriazole (ABT) is a pan-specific, mechanism-based inhibitor of CYP P450 enzymes, often used as co-treatment to investigate the metabolism-dependent toxicity of drugs or chemicals. To assess the confounding effects of ABT in such kind of mechanistic studies, a repeated dose toxicity study with ABT following 7 days oral administration at 0, 25, 50 and 100 mg/kg/day was performed in Wistar rats (5 rats/sex/group). Wistar rat is selected as a model being one of the well characterized rodent species, widely used for toxicity and toxicokinetics studies. The standard parameters of general toxicity study viz. clinical signs, body weight, feed consumption, clinical, gross and histopathology were evaluated. The ABT was tolerated up to the highest tested dose of 100 mg/kg/day. No clinical signs, mortality or effect on feed consumption at any dose. Slight increase in body weight gain was noted in ABT treated females. Increased reticulocyte, and decreased triglycerides, BUN, A/G ratio and plasma potassium; increased weight of liver, kidneys, adrenals and thyroid was noted in ABT treated animals. Microscopically, hypertrophic findings were noted in liver, thyroid, adrenal glands, pituitary and uterus. Some of these changes were observed at as low as 25 mg/kg/day, therefore, NOEL could not be established. Based on this study, it is concluded that ABT is tolerable up to 100 mg/kg/day with some variations in clinical pathology, organ weight and histopathology; these changes should be considered during the assessment of any mechanistic study with ABT. Findings of this manuscript were presented at 58th meeting of the Society of Toxicology, Baltimore, 11 March 2019.



中文翻译:

CYP 抑制剂 1-氨基苯并三唑在 Wistar 大鼠中的短期毒性研究

摘要

1-氨基苯并三唑 (ABT) 是一种泛特异性、基于机制的 CYP P450 酶抑制剂,通常用作共同治疗来研究药物或化学品的代谢依赖性毒性。为了评估 ABT 在此类机制研究中的混杂影响,在 Wistar 大鼠(5 只大鼠/性别/团体)。Wistar 大鼠被选为模型,它是特征良好的啮齿动物之一,广泛用于毒性和毒代动力学研究。一般毒性研究的标准参数即。评估临床症状、体重、饲料消耗、临床、总体和组织病理学。ABT 可耐受高达 100 mg/kg/天的最高测试剂量。在任何剂量下都没有临床症状、死亡率或对饲料消耗的影响。在 ABT 治疗的女性中注意到体重增加略有增加。网织红细胞增加,甘油三酯、BUN、A/G比和血浆钾降低;在接受 ABT 治疗的动物中发现肝脏、肾脏、肾上腺和甲状腺的重量增加。显微镜下,在肝脏、甲状腺、肾上腺、垂体和子宫中发现肥大。其中一些变化在低至 25 mg/kg/天时观察到,因此无法确定 NOEL。根据这项研究,得出的结论是,ABT 可耐受高达 100 mg/kg/天,但临床病理学、器官重量和组织病理学方面存在一些差异;在评估任何 ABT 机制研究期间,应考虑这些变化。这份手稿的调查结果已于 2019 年 3 月 11 日在巴尔的摩举行的毒理学会第 58 次会议上发表。

更新日期:2020-11-29
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