# Potential of Zinc-L-Selenomethionine to Improve the Health of Weaned Piglets and Its Antioxidant Stress Mechanism Through Modulation of PI3K/AKT and Nrf2/Keap1 Signaling Pathways

## TL;DR

Zinc-L-selenomethionine improves the health of weaned piglets by reducing oxidative stress through specific molecular pathways.

## Contribution

This study is the first to investigate the antioxidant mechanisms of Zn-L-SeMet in weaned piglets and intestinal cells.

## Key findings

- Zn-L-SeMet improved growth, antioxidant function, and immune response in piglets.
- Zn-L-SeMet reduced oxidative damage and apoptosis in intestinal cells.
- Zn-L-SeMet activated PI3K/AKT and Nrf2/Keap1 signaling pathways.

## Abstract

Zinc-L-selenomethionine (Zn-L-SeMet), a novel organic selenium (Se) source, shows great potential in alleviating oxidative stress. This study first evaluated the potential of Zn-L-SeMet to improve the health of weaned piglets and investigated underlying molecular mechanisms. In vivo, 240 weaned piglets were assigned to five dietary groups, namely, a control group (basal diet without Se) and four groups supplemented with Zn-L-SeMet (0.1, 0.2, 0.3, or 0.4 mg Se/kg in basal diet) for 42 days. In vitro, an oxidative stress model was established using hydrogen peroxide (H2O2) in porcine intestinal epithelial cells (IPEC-J2) to investigate the mechanisms of Zn-L-SeMet against oxidative damage. The results showed that Zn-L-SeMet improved growth performance, enhanced antioxidant and immune function, stimulated thyroid hormone secretion, and upregulated expression of selenoprotein genes. In vitro, Zn-L-SeMet reduced H2O2-induced apoptosis, promoted IPEC-J2 viability, and enhanced activities of antioxidant enzymes, while reducing lactate dehydrogenase release, malondialdehyde and reactive oxygen species levels. Furthermore, Zn-L-SeMet significantly increased the expression levels of Keap1, NQO1, HO-1, ARE, p-Nrf2, p-PI3K, and p-AKT, and protein ratio of p-Nrf2/Nrf2, PI3K/PI3K, and p-AKT/AKT compared to the H2O2 group (p < 0.05). In conclusion, Zn-L-SeMet improves health status with antioxidant potential in weaned piglets, and the mechanism is associated with activation of PI3K/AKT and Nrf2/Keap1 pathways.