Protective effect of a polysaccharide from Hizikia fusiformis against ethanol-induced cytotoxicity in IEC-6 cells.

In the present study, we examined the signaling pathways related to the ethanol-protective effect of Hf-PS-1 in IEC-6 cells. Ethanol induced the death of IEC-6 cells in a dose-dependent manner, and pretreatment with Hf-PS-1 abrogated the ethanol toxicity. When we examined whether the effect of Hf-PS-1 on ethanol cytotoxicity was associated with insulin growth factor-I receptor signaling pathways, involving mitogen-activated protein kinase (MAPK), we found that ethanol treatment decreased the phosphorylation of Shc and the binding of Grb2 to Shc, and Hf-PS-1 pretreatment increased them. Ethanol treatment also induced the phosphorylation of JNK and ERK, whereas Hf-PS-1 pretreatment decreased JNK activation but not ERK activation. Using a JNK inhibitor (SP600125), we examined GSH levels to determine whether Hf-PS-1 pretreatment mi20 ght protect against ethanol-induced gastric intestinal damage by down-regulating JNK. Co-treatment with SP600125 and ethanol decreased GSH levels, indicating that JNK phosphorylation is a critical factor during ethanol-induced injury and that the effect of Hf-PS-1 occurs via JNK down-regulation. We have thus demonstrated the protective effect of Hf-PS-1 against ethanol-induced cellular damage. Therefore, Hf-PS-1 may be useful as a bio-functional food source to protect against ethanol-induced gastrointestinal injury.