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

Abstract

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.

Acute 1,2-Dichloropropane Poisoning due to Ingestion of Rubber Cement

“…8,9 Besides, the first case of acute toxic encephalopathy caused by occupational exposure to 1,2-DCP was reported in 2018. 5 In animal studies, Wang et al 10 found that 1,2-DCP induced acute liver necrosis due to mitochondrial dysfunction and decreased defense capacity by inhibiting mitochondrial respiratory chain complexes I-IV and glutathione S-transferase 1 (MGST1) activity in mice, and Zhang et al 2 showed that 1,2-DCP affected the expression of proteins with catalytic and carboxylate hydrolase activity by altering liver P450 enzymatic activity. Jin et al 1 showed that exposure to 1,2-DCP induced dermatitis and angiogenesis in the skin of mice by increasing activation of the phosphoinositide 3-kinase/protein kinase-B/mammalian target of rapamycin pathway.…”