Ethyl pyruvate can alleviate alcoholic liver disease through inhibiting Nrf2 signaling pathway

The effects of ethyl pyruvate (EP) on alcoholic liver disease and its related mechanism were investigated. Thirty male C57/BL6 mice were randomly divided to three groups: Control (n=10), alcoholic liver disease (ALD, n=10) and ethyl pyruvate group (EP, n=10). EP group was treated with gavage using EP (100 mg/kg) for 15 consecutive days. Control and ALD group were treated with the same volume of normal saline. After the last gavage, EP and ALD group were treated with the intraperitoneal injection of 50% alcoholic solution (10 ml/kg). After that, ALD and EP group received the gavage using alcohol for 4 weeks, while Control group received the same volume of normal saline, and blood and liver tissues were taken for detection. Results showed that in this experimental study that EP could effectively alleviate the alcoholic liver disease. The levels of alanine aminotransferase (AST), triglycerides (TG), free fatty acid (FFA) and FBG in EP group were significantly lower than those in ALD group, but the number of platelets was reversed, and the differences were statistically significant; the levels of anti-inflammatory factors (TGF-β/IL-10) and superoxide dismutase (SOD) in EP were significantly higher than those in ALP group, but the levels of pro-inflammatory factors (IL-6/TNF-α) and MDA were significantly lower than those in ALP group. EP upregulated CYP2E1, downregulated PPAR-α, nuclear factor 2 (Nrf2) and very-low density lipoprotein receptor (VLDLR), positively regulated the CYP2E1-PPAR-α-ROS signaling pathway and negatively regulated the ROS-Nrf2-VLDLR signaling pathway. EP can increase anti-inflammatory factors and decrease pro-inflammatory factors, enhance the activity of SOD and reduce FFA and TG. Moreover, it can upregulate the PPAR-α expression by negative regulation of CYP2E1-PPAR-α signaling pathway and downregulate the Nrf2 expression by negative regulation of Nrf2-VLDLR signaling pathway, thus alleviating the alcoholic liver disease.