Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis
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 ca...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Veterinary Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2025.1617190/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849737327567437824 |
|---|---|
| author | Zimeng Ma Zimeng Ma Shuo Yan Shuo Yan Huimin Zhang Huimin Zhang Ruilin Du Ruilin Du Xinyue Cheng Xinyue Cheng Siqin Bao Siqin Bao Xihe Li Xihe Li Xihe Li Yongli Song Yongli Song |
| author_facet | Zimeng Ma Zimeng Ma Shuo Yan Shuo Yan Huimin Zhang Huimin Zhang Ruilin Du Ruilin Du Xinyue Cheng Xinyue Cheng Siqin Bao Siqin Bao Xihe Li Xihe Li Xihe Li Yongli Song Yongli Song |
| author_sort | Zimeng Ma |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ca07201a8c0f47bb81f9660079c9b9f6 |
| institution | DOAJ |
| issn | 2297-1769 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj-art-ca07201a8c0f47bb81f9660079c9b9f62025-08-20T03:06:57ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-08-011210.3389/fvets.2025.16171901617190Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axisZimeng Ma0Zimeng Ma1Shuo Yan2Shuo Yan3Huimin Zhang4Huimin Zhang5Ruilin Du6Ruilin Du7Xinyue Cheng8Xinyue Cheng9Siqin Bao10Siqin Bao11Xihe Li12Xihe Li13Xihe Li14Yongli Song15Yongli Song16Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaInner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animal, Hohhot, ChinaResearch Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, ChinaIntroductionCadmium, 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.https://www.frontiersin.org/articles/10.3389/fvets.2025.1617190/fullsheepcadmiumintestine inflammationmitochondrionferroptosisNF-κB signaling |
| spellingShingle | Zimeng Ma Zimeng Ma Shuo Yan Shuo Yan Huimin Zhang Huimin Zhang Ruilin Du Ruilin Du Xinyue Cheng Xinyue Cheng Siqin Bao Siqin Bao Xihe Li Xihe Li Xihe Li Yongli Song Yongli Song Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis Frontiers in Veterinary Science sheep cadmium intestine inflammation mitochondrion ferroptosis NF-κB signaling |
| title | Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis |
| title_full | Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis |
| title_fullStr | Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis |
| title_full_unstemmed | Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis |
| title_short | Cadmium induced ferroptosis and inflammation in sheep via targeting ACSL4/NF-κB axis |
| title_sort | cadmium induced ferroptosis and inflammation in sheep via targeting acsl4 nf κb axis |
| topic | sheep cadmium intestine inflammation mitochondrion ferroptosis NF-κB signaling |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2025.1617190/full |
| work_keys_str_mv | AT zimengma cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT zimengma cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT shuoyan cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT shuoyan cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT huiminzhang cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT huiminzhang cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT ruilindu cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT ruilindu cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT xinyuecheng cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT xinyuecheng cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT siqinbao cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT siqinbao cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT xiheli cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT xiheli cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT xiheli cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT yonglisong cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis AT yonglisong cadmiuminducedferroptosisandinflammationinsheepviatargetingacsl4nfkbaxis |