# Zearalenone Induces Oxidative Stress and Apoptosis in the Jejunum of Weaned Piglets via the p53/Nrf2 Signaling Pathway

## TL;DR

This study shows how zearalenone harms piglet intestines by causing oxidative stress and cell death through specific signaling pathways.

## Contribution

The novel finding is that zearalenone induces intestinal damage via the p53/Nrf2 signaling pathway in weaned piglets.

## Key findings

- Zearalenone reduces antioxidant activity and increases oxidative stress markers in piglet jejunum.
- Zearalenone alters intestinal morphology and mitochondrial structure in weaned piglets.
- Zearalenone affects p53 and Nrf2 pathway gene and protein expression, promoting apoptosis.

## 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.