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