甲基利米达离子液体可能对心脏有毒
Tarek M Abdelghany1, Shireen A Hedya2, Carol De Santis3
1Institute Translational and Clinical Research, Level 4 Leech, Newcastle University, Newcastle Upon Tyne NE2 4HH, United Kingdom; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt; School of Biomedical, Nutritional and Sport Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE24HH, United Kingdom.
Ecotoxicology and environmental safety
|June 5, 2023
概括
甲基利米达离子液体 (MILs) 可以在老鼠中引起心脏毒性,较长的链条更有害. 由于心脏BCRP表达率较高,小鼠的敏感性较低,这表明未来可能存在人类健康风险.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 心血管研究研究心血管研究
背景情况:
- 甲基胺离子液体 (MILs) 是工业溶剂,在环境中越来越多的存在.
- 人类对MILs的潜在暴露需要对其健康影响进行调查.
- 由于其广泛使用,心脏毒性是MILs的一个潜在问题.
研究的目的:
- 在老鼠模型中评估各种甲基胺离子液体 (MIL) 的心脏毒性.
- 为了比较MILs与不同链长度的心脏毒性作用.
- 为了研究老鼠和小鼠之间MIL心脏毒性的物种特异性差异.
主要方法:
- 在实验室中对MILs对大鼠新生儿心肌细胞功能和存活率的评估.
- 亚急性和慢性口服/饮用水毒性研究,对长链MILs的老鼠进行.
- 在老鼠和小鼠心脏中进行基因和蛋白质表达分析 (qRT-PCR,西方涂抹).
- 药理上抑制小鼠心肌细胞细胞系中的特定载体 (BCRP,P-糖蛋白).
主要成果:
- 增加MIL的基链长度与增加的心脏毒性相关.
- 长链MILs (HMI,M8OI,DMI) 在老鼠中诱导心脏毒性,通过临床化学和组织病理学证实.
- 与老鼠心脏相比,老鼠心脏表现出明显更高的BCRP和P-葡萄糖蛋白-3表达.
- 抑制BCRP部分使小鼠心肌细胞对MILs敏感,这表明在物种差异中发挥了作用.
结论:
- 甲基利米达离子液体 (MILs) 具有心脏毒性风险,特别是在老鼠中.
- 较高的心脏BCRP表达在小鼠中可能会产生对MIL诱导的心脏毒性的抗性.
- MILs代表了潜在的未来人类健康危险,对心血管疾病易感性的影响尚不清楚.
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