ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Animal Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1617190
Cadmium Induced Ferroptosis and Inflammation in Sheep via Targeting ACSL4/NF-κB Axis
Provisionally accepted
- Inner Mongolia University, Hohhot, China
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Cadmium, a major environmental contaminant, induces progressive intestinal damage through bioaccumulation in vivo. Elucidating its pathogenic mechanisms is crucial for developing therapeutic interventions. This study employed multi-omics approaches to systematically investigated cadmium-induced ileal dysfunction in Hu sheep and the intervention mechanisms of sodium octanoate. Phenotypic 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. Our findings establish the ACSL4/NF-κB axis as a central mechanism in cadmium-induced 行距: 2 倍行距 设置格式[tom_lucky boy]: 删除[梓萌 马]:
Keywords: sheeep;, Cadmium, Intestine inflammation, mitochondrion, ferroptosis, NF-κB signaling, Sodium octanoate
Received: 24 Apr 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Ma, Yan, Zhang, Ruilin, Cheng, Bao, Li and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yongli Song, Inner Mongolia University, Hohhot, China
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