Alginate Oligosaccharides Attenuate Heat Stress-Induced Intestinal Ferroptosis in Broilers: Association with Nrf2/SLC7A11/GPX4 Signaling

This study investigated the effects of alginate oligosaccharides (AOS) on intestinal ferroptosis of broilers under heat stress (HS) and revealed possible mechanisms. In broilers under HS, dietary 600 mg/kg AOS alleviated intestinal ferroptosis-like mitochondrial abnormalities and iron deposition, and attenuated selected Fe2+ and lipid-peroxidation indices in a segment-dependent manner. Dietary AOS also counteracted HS-induced transcriptional changes related to iron handling and lipid peroxidation-associated processes, with the most prominent protection observed in the jejunum. AOS enhanced jejunal Nrf2 phosphorylation and increased SLC7A11 and GPX4 protein abundance, indicating AOS was associated with restoration of Nrf2/SLC7A11/GPX4 signaling. Using primary chicken small intestinal epithelial cells as an in vitro model, AOS at 10 μg/mL showed similar protective effects with ferroptosis inhibitor Ferrostatin-1, whereas cotreatment with Nrf2 inhibitor ML385 weakened the mitigation effects of AOS on ferroptosis and SLC7A11/GPX4 expression. These findings indicate that AOS attenuates HS-induced intestinal ferroptotic injury and this protection is associated with Nrf2/SLC7A11/GPX4 signaling.