Gly-Pro-Ala peptide and FGSHF3 exert protective effects in DON-induced toxicity and intestinal damage via decreasing oxidative stress

Deoxynivalenol (DON), a common mycotoxin, usually induces oxidative stress and intestinal injury of humans and animals. This study aims to investigate the protective effect of Gly-Pro-Ala (GPA) peptide, isolated from fish skin gelatin hydrolysate fraction 3 (FGSHF3), on alleviating the toxicity and oxidative stress induced by DON in the mice and IPEC-J2 cells. DON treatment decreases average daily gain and feeds intake, which causes enlargement of the liver and spleen. FGSHF3 (200 mg/kg) and GPA (200 mg/kg) treatment significantly increase average daily gain and inhibits enlargement of the liver and spleen. Furthermore, FGSHF3 and GPA treatment significantly alleviates intestinal injury and maintains tight junction in mice and IPEC-J2 cells. FGSHF3 and GPA treatment significantly inhibits ROS and MDA production and enhances antioxidant enzyme activity, such as CAT, SOD-1, GCLM, GCLC, and GSH-PX. Furthermore, FGSHF3 and GPA treatment promote Nrf2 migration from the cytoplasm to the nucleus, resulting in exerting antioxidant effects. And its effects are abolished after Nrf2 is knockdown by siRNA. Overall, our results suggest GPA peptide may be a promising candidate for the alleviation of DON-induced toxicity in humans and animals.