Background: Liver ischemia reperfusion injury (LIRI) is a common problem during surgical procedures of the liver. It causes severe inflammatory responses and cell death, eventually leading to serious liver damage. Agmatine (AGM) is an endogenous polyamine with analgesic, anti-inflammatory, and antiapoptotic effects. However, it is still unknown whether AGM can protect the liver from damage caused by LIRI.
Methods: For the in vivo experiments, a mouse model of partial warm hepatic ischemia reperfusion was established using C57BL/6J mice and then serum transaminase concentrations were analyzed. Histopathology was used to evaluate the degree of liver injury and quantitative real-time PCR was used to measure the amount of inflammatory cytokines. For the in vitro experiments, a cellular model of cobalt chloride (CoCl2)-induced hypoxia was established using AML12 cells. Flow cytometry was performed to measure the apoptosis levels. Western blotting analysis was conducted to measure the levels of proteins involved in apoptosis and Wnt/β-catenin signaling. We also chose 2 inhibitors of the Wnt/β-catenin signaling to elucidate the relationship between AGM and the Wnt/β-catenin signaling.
Results: AGM showed protective effects against LIRI-induced liver damage, inflammatory responses, and cell apoptosis along with alleviation of CoCl2-induced hepatocyte injury. AGM activated the Wnt/β-catenin signaling pathway during LIRI and CoCl2-induced hepatocyte injury; however, when the Wnt/β-catenin pathway was inhibited, the protective effects of AGM declined.
Conclusions: AGM showed protective effects against LIRI by activating the Wnt/β-catenin signaling pathway.