AUTHOR=Ma Zimeng , Yan Shuo , Zhang Huimin , Du Ruilin , Cheng Xinyue , Bao Siqin , Li Xihe , Song Yongli 

TITLE=Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis

JOURNAL=Frontiers in Veterinary Science

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1617190

DOI=10.3389/fvets.2025.1617190

ISSN=2297-1769

ABSTRACT=IntroductionCadmium, a major environmental contaminant, induces progressive intestinal damage through bioaccumulation in vivo. Elucidating its pathogenic mechanisms is crucial for developing therapeutic interventions.MethodsThis study employed multi-omics approaches to systematically investigated cadmium-induced ileal dysfunction in Hu sheep and the intervention mechanisms of sodium octanoate.ResultsPhenotypic assessment revealed cadmium exposure caused intestinal barrier impairment and histopathological changes. Integrated transcriptomic-proteomic analysis revealed cadmium disrupted mitochondrial dysfunction via oxidative phosphorylation pathway inhibition. Leading to reactive oxygen species (ROS) overaccumulation. This ROS surge activated ferroptosis, which exacerbated inflammatory responses through NF-κB signaling. Cross-omics correlation analysis identified ferroptosis-related proteins as key regulators of the NF-κB inflammatory axis, suggesting ferroptosis modulation as a potential therapeutic strategy. Notably, sodium octanoate exhibited potent anti-inflammatory effects through specific binding to ACSL4, a critical ferroptosis regulatory protein, this interaction ameliorated oxidative stress and inflammation cascades while demonstrating therapeutic potential for cadmium-induced inflammation.DiscussionOur findings establish the ACSL4/NF-κB axis as a central mechanism in cadmium-induced pathology, highlighting sodium octanoate as a potential therapeutic intervention for pollutant-induced intestinal disorders.