Veratric acid alleviates liver ischemia/reperfusion injury by activating the Nrf2 signaling pathway.

Oxidative stress following liver ischemia/reperfusion (I/R) is an important pathological mechanism responsible for liver injury. Veratric acid (VA) is a phenolic benzoic acid that has been reported to have antioxidant properties. However, whether VA has protective effects against liver I/R injury remains unclear. In the present study, a mouse liver I/R injury model was established. VA was administered intragastrically for one week before liver I/R. Biochemical indicators, histological analysis, cell apoptosis, oxidative stress, and pathway proteins were tested to evaluate the protective effects of VA on liver I/R injury. Furthermore, a mouse AML12 hepatocyte hypoxia/reoxygenation (H/R) model was used to explore the underlying mechanism. VA alleviated liver I/R injury, as manifested by decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrotic area, oxidative stress, and hepatocyte apoptosis. VA pretreatment increased the expression of Nrf2 and its downstream antioxidant proteins heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO-1). In addition, VA pretreatment increased AML12 cell activity and decreased oxidative stress; it also decreased the apoptosis induced by H/R. Moreover, the protective effect of VA on hepatocytes was related to the activation of the Nrf2 signaling pathway, and to increases in the Nrf2, HO-1, and NQO-1 protein expression. The inhibition of Nrf2 with ML385 offseted VA-mediated protection in AML12 cells. In conclusion, these results suggest that VA protects the liver from oxidative stress and apoptosis induced by liver I/R injury by activating the Nrf2 signaling pathway.