# Selenoprotein M Protects Intestinal Health in Nickel-Exposed Mice: Implications for Animal Welfare Under Heavy Metal Stress

## TL;DR

This study shows that selenoprotein M helps protect the intestines of mice from damage caused by nickel exposure, which could improve animal health in polluted environments.

## Contribution

The study reveals that SelM deficiency worsens nickel-induced colonic damage by failing to suppress oxidative stress and autophagy.

## Key findings

- Nickel exposure increases ROS and triggers inflammation in the colon, with SelM knockout mice showing more severe effects.
- SelM reduces oxidative stress and controls inflammation, protecting the gut from nickel-induced damage.
- Inhibiting oxidative stress or autophagy reduced inflammation in nickel-exposed mice.

## Abstract

Heavy metal pollution poses a growing challenge to both human and animal health. Nickel, although required in trace amounts, becomes harmful when present in excess, particularly affecting the digestive system. In this study, we investigated how a specific selenium-containing protein, called selenoprotein M (SelM), protects the colon when animals are exposed to nickel. We used mice that lacked SelM as well as normal mice, and we also carried out cell culture experiments. Our results showed that nickel exposure caused damage in the colon by increasing harmful molecules known as reactive oxygen species, overstimulating a cellular process called autophagy, and triggering inflammation. These harmful changes were much stronger in animals without SelM. On the other hand, SelM helped maintain a healthier balance in the colon by reducing oxidative stress and controlling inflammation. These findings suggest that selenium and its related proteins may help protect the gut against heavy metal pollution. Such insights are valuable for improving animal health and welfare, and they may also be useful for developing strategies to safeguard livestock production under environmental stress.

Nickel (Ni) is a heavy metal element and environmental pollutant that significantly threatens human health. Selenoprotein M (SelM) is a selenium-containing protein with antioxidant properties. However, the role of SelM deficiency in Ni -induced colonic tissue damage in mice remains unclear. To address this, in vivo and in vitro models were established, including SelM knockout (SelM(−/−)) and/or nickel chloride (NiCl2)-treated mice. In vitro, an MCEC model was used to establish Ni exposure and SelM knockdown conditions. The results showed that NiCl2 induced significant inflammatory cell infiltration and lesions in the microstructure of the mouse colon. Additionally, Ni exposure was found to enhance the production of reactive oxygen species (ROS) in mice’s colonic tissue, activating oxidative stress, which in turn led to the formation of autophagosomes and the onset of inflammation. Significantly, SelM knockout exacerbated these outcomes. The oxidative stress inhibitor NAC and the autophagy inhibitor 3-MA were introduced to elucidate the underlying mechanisms further. The results showed that autophagy was reduced following NAC treatment, and inflammation was alleviated after 3-MA administration. Taken together, these findings suggest that SelM alleviated Ni -induced colonic inflammation in mice through suppression of oxidative stress-mediated excessive autophagy.