Ferulic acid protects against gamma-radiation induced liver injury via regulating JAK/STAT/Nrf2 pathways

This study aims to evaluate the effect and underlying mechanism of ferulic acid (FA) in alleviating the acute liver injury by ionizing radiation (IR) in vivo. Rats were divided into 4groups (Groups: control, 6Gy irradiated (IRR), FA (50 mg/kg) and FA + IRR). The results showed that FA can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, FA prevented IR-induced liver fibrosis and blocked the JAK/STAT signaling pathway to effectively inhibit the hepatic inflammatory response; and inhibited IR-induced oxidative stress (OS) by upregulating the Nrf2 signaling pathway and promoting the synthesis of several antioxidants. Moreover, FA inhibited ferroptosis in the liver by stimulating the expression of GPX4 and SLC7A11. FA reduced lipid peroxidation by downregulation of the reactive oxygen species (ROS) production and iron aggregation, thus inhibiting ferroptosis and alleviating IR-induced liver injury. In conclusion, the current study suggests the potential complex mechanisms underlying the mitigating impact of FA in IR-induced ferroptotic liver damage. [Display omitted] •Reactive oxygen species induced by radiation can attack different hepatic cell components and induce ferroptosis.•Ferulic acid prevented irradiation-induced liver fibrosis and blocked the JAK/STAT signaling pathway.•Ferulic acid upregulated Nrf2 signaling pathway and promoted the synthesis of several antioxidants.•Ferulic acid inhibited ferroptosis in the liver by stimulating the expression of GPX4 and SLC7A11.