Protective potential effects of fucoidan in hepatic cold ischemia-rerfusion injury in rats

The necessity to increase the efficiency of organ preservation has pushed physicians to consider the use of pharmacological additives in preservation solutions to minimize ischemia reperfusion injury. Here, we evaluated the effect of fucoidan, sulfated polysaccharide from brown seaweed, as an additive to IGL-1 (Institut Georges Lopez) preservation solution. Livers from Wistar rats were preserved for 24 h at 4 °C in IGL-1 solution, enriched or not with fucoidan (100 mg/L). Thereafter, they were subjected to reperfusion (2 h, at 37 °C) using an isolated perfused rat liver model. The addition of fucoidan to IGL-1 solution reduced hepatic injury (AST, ALT) and improved liver function compared to IGL-1 solution without fucoidan. In addition, we noted a significant increase in the phosphorylation of AMPK, AKT protein kinase and GSK3-β, leading to a reduction in VDAC phosphorylation, as well as a reduction in apoptosis (caspase 3), mitochondrial damage, oxidative stress and endoplasmic reticulum (ER) stress markers. Furthermore, ERK1/2 and P38 MAPKs phosphorylation significantly decreased after supplementation of IGL-1 solution with fucoidan.In conclusion, the supplementation of IGL-1 solution with fucoidan maintained liver graft integrity and function through the prevention of the ER stress, oxidative stress and mitochondrial dysfunction. Fucoidan could be considered as potential natural therapeutic agent to alleviate graft injury.