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Renal injury and hepatic effects from the methylimidazolium ionic liquid M8OI in mouse.
Ecotoxicology and Environmental Safety ( IF 6.8 ) Pub Date : 2020-07-04 , DOI: 10.1016/j.ecoenv.2020.110902
Alistair C Leitch 1 , Tarek M Abdelghany 2 , Alex Charlton 3 , Justina Grigalyte 4 , Fiona Oakley 5 , Lee A Borthwick 5 , Lee Reed 5 , Amber Knox 5 , William J Reilly 5 , Loranne Agius 6 , Peter G Blain 6 , Matthew C Wright 1
Affiliation  

The ionic liquid 1-octyl-3-methylimidazolium (M8OI) has been found in the environment and identified as a hazard for triggering the liver disease primary biliary cholangitis (PBC). Given limited toxicity data for M8OI and other structurally-related ionic liquids, target organs for M8OI toxicity were examined. Adult male C57Bl6 mice were acutely exposed to 0–10 mg/kg body weight M8OI via 2 intraperitoneal injections (time zero and 18 h) and effects examined at 24 h. At termination, tissue histopathology, serum and urinary endpoints were examined. No overt pathological changes were observed in the heart and brain. In contrast, focal and mild to multifocal and moderate degeneration with a general trend for an increase in severity with increased dose was observed in the kidney. These changes were accompanied by a dose-dependent increased expression of Kim1 in kidney tissue, marked elevations in urinary Kim1 protein and a dose-dependent increase in serum creatinine. Hepatic changes were limited to a significant dose-dependent loss of hepatic glycogen and a mild but significant increase in portal tract inflammatory recruitment and/or fibroblastic proliferation accompanied by a focal fibrotic change. Cultured mouse tissue slices reflected these in vivo effects in that dose-dependent injury was observed in kidney slices but not in the liver. Kidney slices accumulated higher levels of M8OI than liver slices (e.g. at 10 μM, greater than 4 fold) and liver slices where markedly more active in the metabolism of M8OI. These data indicate that the kidney is a target organ for the toxic effects of M8OI accompanied by mild cholangiopathic changes in the liver after intraperitoneal administration.



中文翻译:

甲基咪唑鎓离子液体M8OI对小鼠的肾脏损伤和肝效应。

离子液体1-辛基-3-甲基咪唑鎓(M8OI)已在环境中发现,并被确定为引发肝脏疾病的原发性胆源性胆管炎(PBC)的危害。鉴于M8OI和其他与结构相关的离子液体的毒性数据有限,因此检查了M8OI毒性的靶器官。成年雄性C57Bl6小鼠通过2次腹膜内注射(零时和18小时)急性暴露于0-10 mg / kg体重M8OI,并在24 h时检查其作用。终止时,检查组织病理学,血清和尿终点。在心脏和大脑中未观察到明显的病理变化。相反,在肾脏中观察到局灶性和轻度至多灶性和中度变性,并且总体趋势是随着剂量增加而严重性增加。这些变化伴随着肾组织中Kim1的剂量依赖性增加表达,尿中Kim1蛋白的显着升高以及血清肌酐的剂量依赖性增加。肝变化仅限于肝糖原的显着剂量依赖性损失以及伴随局灶性纤维化变化的门静脉炎性募集和/或成纤维细胞增生的轻度但显着增加。培养的小鼠组织切片反映了这些肾脏切片中观察到剂量依赖性损伤的体内效应,但在肝脏中未观察到。肾脏切片积累的M8OI水平高于肝脏切片(例如10μM,大于4倍)和肝脏切片,后者在M8OI代谢中的活性更高。这些数据表明,在腹膜内给药后,肾脏是M8OI毒性作用的靶器官,并伴有肝脏轻度胆管病变。

更新日期:2020-07-05
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