Acute inhalation co-exposure to 1,2-dichloropropane and dichloromethane cause liver damage by inhibiting mitochondrial respiration and defense ability in mice

作者：Wang, Hufei; Chen, Jiamin; Suda, Megumi; Yanagiba, Yukie; Weng, Zuquan^*; Wang, Rui-Sheng^*

来源：Journal of Applied Toxicology, 2019, 39(2): 260-270.

DOI：10.1002/jat.3715

• 1,2-dichloropropane
• dichloromethane
• microsomal glutathione s-transferase 1
• mitochondrial dysfunctions
• hepatocellular necrosis

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 glutathione S-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.

• 出版日期2019-2
• 单位福州大学; 国家安全生产监督管理总局信息研究院