Zearalenone Induces Oxidative Stress and Apoptosis in the Jejunum of Weaned Piglets via the p53/Nrf2 Signaling Pathway
Yihao Sang, Shaojin Hou, Zhongfang Zhang, Shuzhen Jiang +2
AI summary
75% confidenceThis study demonstrates that dietary Zearalenone exposure in weaned piglets induces significant oxidative stress and apoptosis in the jejunum despite having no observable impact on production performance. The mechanism involves the activation of the p53/Nrf2 signaling pathway, characterized by increased expression of pro-apoptotic markers like Bax and Caspase1 alongside reduced antioxidant enzyme activities. Morphological damage included villus atrophy, crypt hyperplasia, and severe mitochondrial dysfunction.
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Abstract
This study investigated the mechanisms by which ZEA induces oxidative stress and apoptosis in the jejunum of piglets and explored the roles of the tumor suppressor gene p53 and nuclear factor E2-related factor 2 (Nrf2) signaling pathways. Twelve weaned piglets were randomized into Control (basal diet) and ZEA groups (basal diet + 1.0 mg/kg ZEA; 6 piglets/group). No differences were observed between the control and ZEA groups for all production performance indicators. Compared with the jejunum of the control group, the ZEA group exhibited reduced levels of total superoxide dismutase, glutathione peroxidase activity, and total antioxidant capacity, along with elevated malondialdehyde content. Morphological examination revealed increased crypt depth and decreased villus height and villus-to-crypt ratio, as well as swollen, vacuolated spherical mitochondria with disrupted cristae. Immunohistochemistry showed enhanced p53 and Nrf2 immunoreactivity. The relative mRNA levels of Nrf2, Ho1, Gpx1, Cytc1, p53, Caspase1, and Bax increased. The Bax/Bcl-2 ratio increased, and Keap1 and Bcl-2 mRNA levels decreased. The relative protein levels of Nrf2, p53, Bax, Caspase1, and Gpx1 increased, whereas that of Bcl-2 decreased. All differences were significant at p 0.05. Dietary supplementation with ZEA altered the morphological structure of intestinal tissues and mitochondria. By affecting the expression of genes related to the p53 and Nrf2 signaling pathways, it induces intestinal oxidative stress and apoptosis, thereby impairing intestinal health in weaned piglets.
Key findings
- ZEA exposure significantly reduced total superoxide dismutase, glutathione peroxidase activity, and total antioxidant capacity while elevating malondialdehyde content.
- Histological analysis revealed increased crypt depth, decreased villus height, a lower villus-to-crypt ratio, and swollen mitochondria with disrupted cristae.
- Gene expression analysis showed upregulation of p53, Nrf2, Bax, Caspase1, and Cytc1, along with downregulation of Keap1 and Bcl-2.
Keywords
Identifiers
- Journal
- International Journal of Molecular Sciences
- Year
- 2026