Emerging risk from "environmentally-friendly" solvents: Interaction of methylimidazolium ionic liquids with the mitochondrial electron transport chain is a key initiation event in their mammalian toxicity
Emerging risk from "environmentally-friendly" solvents: Interaction of methylimidazolium ionic liquids with the mitochondrial electron transport chain is a key initiation event in their mammalian toxicity
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DOI：
10.1016/j.fct.2020.111593
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发表时间：
2020-11-01
影响因子：
4.3
通讯作者：
Wright, Matthew C.
中科院分区：
文献类型：
--
作者：
Abdelghany, Tarek M.;Leitch, Alistair C.;Wright, Matthew C.
最近的研究已经确定了8C烷基链甲基咪唑离子液体1-辛基1-3-甲基咪唑在环境中及其引发自身免疫性肝病原发性胆管炎的潜力。因此，研究了一系列甲基咪唑离子液体的毒性。氧消耗被迅速抑制，并且随着烷基链的长度而增加。这先于caspase 3/7诱导和DNA断裂。染料还原能力的时间和剂量依赖性损失反映了这些影响，2C和10C烷基链液体的效力差异为bb0 - 700倍。没有离子液体直接抑制线粒体复合物I-IV或复合物V （f0f1 - atp酶）。然而，二亚硝酸盐还原和ESR光谱研究表明，在甲基咪唑离子液体的存在下，氧的一个电子还原，这表明甲基咪唑离子液体具有线粒体电子受体的功能。然而，只有长链离子液体在水生理条件下形成非水相或胶束，并导致完整细胞中活性氧的增加。因此，这些数据表明，长链甲基咪唑液体对敏感的肝祖细胞是有毒的，因为它们很容易在线粒体内膜内整合并接受电子链中的电子，导致氧化应激。
Recent studies have identified the 8C alkyl chain methylimidazolium ionic liquid 1-octy1-3-methylimidazolium in the environment and its potential to trigger the auto-immune liver disease primary biliary cholangitis. The toxicity of a range of methylimidazolium ionic liquids were therefore examined. Oxygen consumption was rapidly inhibited, with potency increasing with alkyl chain length. This preceded caspase 3/7 induction and DNA fragmentation. Time- and dose-dependent loss of dye reduction capacities reflected these effects, with a >700 fold difference in potency between 2C and 10C alkyl chain liquids. None of the ionic liquids directly inhibited mitochondrial complexes I-IV or complex V (F0F1-ATPase). However, dithionite reduction and ESR spectroscopy studies indicate a one electron reduction of oxygen in the presence of a methylimidazolium ionic liquid, suggesting methylimidazolium ionic liquids function as mitochondrial electron acceptors. However, only longer chain ionic liquids form a non-aqueous phase or micelle under aqueous physiological conditions and lead to increases in reactive oxygen species in intact cells. These data therefore suggest that the longer chain methylimidazolium liquids are toxic in sensitive liver progenitor cells because they both readily integrate within the inner mitochondrial membrane and accept electrons from the electron chain, leading to oxidative stress.