Acute inhalation co-exposure to 1,2-dichloropropane and dichloromethane cause liver damage by inhibiting mitochondrial respiration and defense ability in mice.
Acute inhalation co-exposure to 1,2-dichloropropane and dichloromethane cause liver damage by inhibiting mitochondrial respiration and defense ability in mice.
复制标题
急性吸入同时接触 1,2-二氯丙烷和二氯甲烷会抑制小鼠线粒体呼吸和防御能力，从而导致肝损伤。
DOI：
10.1002/jat.3715
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Wang RS.
中科院分区：
文献类型：
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作者：
Wang H;Chen J;Suda M;Yanagiba Y;Weng Z;Wang RS.
1，2-二氯丙烷(1，2-DCP)被用作工业溶剂、杀虫剂熏蒸剂和家用干洗产品。长期接触1，2-二氯苯酚引起的致癌性是公认的。然而，与急性吸入暴露1，2-DCP有关的可能的肝脏损害和相关的毒性机制很少有报道。在这项研究中，我们研究了1，2-DCP和二氯甲烷(DCM)单独和联合暴露对小鼠肝脏的影响。结果表明，1，2-DCP可引起大鼠肝脏明显坏死，其机制可能与1，2-DCP抑制线粒体呼吸链复合体I-IV活性，导致线粒体功能障碍和过度消耗ATP有关。此外，1，2-DCP还通过抑制线粒体谷胱甘肽转移酶1(MGST1)活性，降低线粒体防御能力，进一步加重肝损伤。此外，我们还发现，DCM联合暴露可能会增强1，2-DCP的毒性。我们的研究结果表明，线粒体功能和MGST1活性的抑制在1，2-DCP诱导的肝损伤的调节中起着关键作用。此外，我们的结果有助于研究线粒体主导的信号通路在1，2-DCP和DCM诱导的肝损伤中的新机制。
1,2‐Dichloropropane (1,2‐DCP) is used as an industrial solvent, insecticide fumigant and household dry cleaning product. Carcinogenicity caused by long‐term exposure to 1,2‐DCP is well established. However, the possible liver damage and related toxic mechanisms associated with acute inhalation exposure to 1,2‐DCP are rarely reported. In this study, we investigated the effects of individual and combined exposure to 1,2‐DCP and dichloromethane (DCM) on mice liver. The results showed that 1,2‐DCP significantly caused liver necrosis, possibly due to 1,2‐DCP‐induced inhibition of the mitochondrial respiratory chain complex I‐IV activities, resulting in mitochondrial dysfunction and extreme ATP consumption. Moreover, 1,2‐DCP also decreased mitochondrial defense ability by inhibiting the mitochondrial glutathioneS‐transferase 1 (MGST1) activity, further aggravating liver damage. Additionally, we found that DCM co‐exposure potentially enhanced 1,2‐DCP toxicity. Our findings suggest that inhibition of mitochondrial function and MGST1 activity play critical roles in modulating 1,2‐DCP‐induced liver damage. Furthermore, our results contribute to study the new mechanism of mitochondria‐dominated signaling pathways underlying liver injury induced by 1,2‐DCP and DCM.