Allicin attenuated hepatic ischemia/reperfusion injury in mice by regulating PPAR gamma-IRAK-M-TLR4 signal pathway

Background: Hepatic ischemia/reperfusion (I/R) injury to the liver is a significant cause of morbidity and mortality following liver surgery, trauma, and hemorrhagic shock. It was reported that allicin, a type of garlic compound, had a protective effect against other hepatic diseases. Allicin's ability to protect against liver injury caused by ischemic reperfusion remains unknown. As a result, we conducted this study to determine allicin's effects and mechanism of action in hepatic I/R injury. Method: The liver I/R injury model was established by clamping the blood supply to the left and middle liver lobes. Three days prior to the hepatic I/R injury, different concentrations of allicin were gavaged. Then, hepatic function, histological changes, apoptosis markers, oxidative stress, and inflammatory cytokines were measured, and the molecular mechanisms were evaluated using western blot. Another separation experiment used IRAK-M knockout mice and peroxisome proliferator-activated receptor-gamma (PPAR gamma) inhibitor to deduce the molecular mechanisms. Results: Pretreatment with allicin prior to hepatic I/R injury reduced liver damage by inhibiting aminotransferase activity and alleviating liver injury. It significantly decreased cell apoptosis, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) production, and hepatic oxidative stress. Furthermore, this study demonstrated that GW9662 (inhibitor of PPAR gamma) abrogated allicin's positive effect by inhibiting PPAR gamma expression while suppressing IRAK-M expression. Thus, the depletion of IRAK-M cannot influence the expression of PPAR gamma. The down-regulation of PPAR gamma-IRAK-M disabled the protection of allicin in I/R injury. Conclusion: Allicin protects against hepatic I/R injury via dose-dependent regulation of the PPAR gamma-IRAK-M-TLR4 signaling pathway, and it may be a potential drug in future clinical treatment.