Time-course and molecular mechanism of hepatotoxicity induced by 1,3-dichloro-2-propanol in rats

•1,3-DCP causes oxidative hepatic damage in rats.•Oxidative hepatic damages peak at 12 h after 1,3-DCP treatment.•1,3-DCP increases hepatocellular apoptosis and nuclear Nrf2 expression.•1,3-DCP activates oxidative stress-mediated MAPK.

This study investigated the time-course of 1,3-dichloro-2-propanol (1,3-DCP)-induced hepatotoxicity and the molecular mechanism of its oxidative stress and apoptotic changes in rats. Thirty-six male rats were randomly assigned to six groups of six rats each and were administered a single oral dose of 1,3-DCP (90 mg/kg) or its vehicle. 1,3-DCP caused acute hepatic damage, as evidenced by marked increases in serum aminotransferase, alkaline phosphatase, and histopathological alterations. These functional and histopathological changes in the liver peaked at 12 h after administration and then decreased progressively. Oxidative stress indices were increased significantly at 6 h, peaked at 12 h, and then decreased progressively. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)- and caspase-3-positive cells increased after 6 h, peaked at 12 and 24 h, and then decreased. The protein levels of phosphorylated mitogen-activated protein kinases (MAPKs) including p-Erk1/2 and p-JNK showed a similar trend to the numbers of TUNEL- and caspase-3-positive cells. These results indicate that 1,3-DCP increases oxidative stress, nuclear translocation of Nrf2, and expression of Nrf2-targeted genes, followed by increased functional and histopathological alterations in the liver. The increase in hepatocellular apoptosis induced by 1,3-DCP may be related to oxidative stress-mediated MAPK activation.