Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treat-ment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the free iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) ex-pressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.

Automated summary

This study investigates the effects of fucoidan on iron overload and ferroptosis-induced liver injury caused by alcohol exposure. The results show that fucoidan treatment can protect against liver damage, reduce iron deposition, and alleviate ferroptosis. Fucoidan regulates the hepcidin-intestinal DMT1/FPN1 axis and upregulates the p62/Nrf2/SLC7A11 pathway to inhibit iron overload and cell death.