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 treatment 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) expressions 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.

Effects of resistant starch supplementation on oxidative stress and inflammation biomarkers: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Animal experiments showed that resistant starch (RS) had an antioxidant and antiinflammatory effect. However, clinical studies showed both insignificant and significant effects of RS on inflammation and oxidative stress. The purpose of this work is to conduct a systematic review and meta-analysis of previous randomized controlled trials (RCTs) to investigate these effects. METHODS AND STUDY DESIGN: A systematic literature search was conducted on Web of Science, Scopus, PubMed and Cochrane electronic databases, which included studies from the earliest date of the database to September 2021. Key inclusion criteria were: RCTs; reporting at least one inflammatory or oxidative stress biomarker as endpoint; more than seven day intervention. Key exclusion criteria were: using a mixture of RS and other functional food ingredients as intervention substance; inappropriate controls. RESULTS: A total of 16 RCTs including 706 subjects were included. RS supplementation significantly improved total antioxidant capacity [standard mean difference (SMD) (95% CI): 2.64 (0.34, 4.94), p=0.03], and significantly reduced blood malondialdehyde concentration [SMD (95% CI): -0.55 (- 0.94, -0.17), p=0.01]. RS supplementation significantly reduced blood C-reactive protein concentration in type 2 diabetes mellitus (T2DM) patients [SMD (95% CI): -0.35 (-0.65, -0.05), p=0.02]. RS consumption significantly reduced blood interlukin-6 and tumor necrosis factor- concentration if removing one distinct trial. CONCLUSIONS: RS supplementation may significantly reduce a few oxidative-stress and inflammation biomarkers such as malondialdehyde and C-reactive protein, particularly in T2DM patients. Future work should investigate the optimal dosage of RS supplementation for modulating oxidative stress and inflammation biomarkers related to T2DM.