Subacute ruminal acidosis induces hepatic injury in dairy goats via oxidative stress and ferritinophagy-ferroptosis axis Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1016/j.intimp.2025.115026
Increasing the proportion of high-concentrate feed in ruminant diets can rapidly enhance milk production and overall performance. Prolonged feeding of high-concentrate (HC) diet may reduce ruminal pH, potentially inducing subacute rumen acidosis (SARA). Large amounts of lipopolysaccharide (LPS) are produced and enter the bloodstream through the damaged rumen barrier, accumulating in the liver tissue, causing inflammation. Studies indicate LPS can induce liver injury in mice through ferroptosis activation. However, the relationship between SARA-induced rumen-derived LPS liver injury and ferroptosis remains unclear. In this study, HC feeding of dairy goats established SARA model, revealing increased liver inflammation, disrupted barrier integrity, and significant changes in oxidative stress markers. 16S rRNA demonstrated that rumen microbiota disruption in the HC group. To determine whether SARA-induced liver injury in dairy goats resulted from disrupted microbiota, rumen microbiota was transplanted into mice, inducing liver injury via activation of the ferritinophagy-ferroptosis axis. In vitro LPS stimulation of AML12, the primary harmful component of the disturbed rumen microbiota, significantly elevated the level of oxidative stress and activate ferritinophagy-ferroptosis axis to up-regulate the level of inflammation. Ferrostatin-1 (Fer-1) inhibition of ferroptosis markedly reduced inflammation level. This study demonstrates that rumen-derived LPS from HC diets triggers hepatic injury through oxidative stress mediated activation of the ferroptosis-ferritinophagy axis, thereby elucidating a novel molecular mechanism underlying HC-induced liver pathology in dairy goats.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.intimp.2025.115026
- OA Status
- hybrid
- Cited By
- 3
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411046782