Selenium alleviates cadmium-induced aging via mitochondrial quality control in the livers of sheep

Cadmium (Cd) is a heavy metal with toxicity that induces mitochondrial dysfunction and aging, and selenium (Se) can alleviate its toxicity. However, the underlying mechanism of Se alleviating Cd-induced aging in sheep livers deserves further study. This study was to explore the protective mechanism of Se on the Cd-induced aging in the livers of sheep. A total of forty-eight sheep weighing about 10 kg were randomly divided into four groups: control group, Se group [0.34 mg Se·kg^-1·body weight (BW)], Cd group (1 mg Cd·kg^-1·BW), and Se + Cd group (0.34 mg Se·kg^-1·BW +1 mg Cd·kg^-1·BW). The results showed that Cd caused vacuolization, granule denaturation, and mitochondrial vacuolization in hepatocytes. Furthermore, the levels of catalase (CAT), total superoxide dismutase (T-SOD), glutathione (GSH) and adenosine triphosphate (ATP) in liver mitochondria were down-regulated, but the levels of hydrogen peroxide (H₂O₂) and malonaldehyde (MDA) were up-regulated under Cd treatment. Besides, the cyclin-dependent kinase inhibitor 1 (P21) immunohistochemistry positive signal and the puncta of immunofluorescence co-locations of E3 ubiquitin ligase Parkin (Parkin)/ cytochrome c oxidase IV (COX IV) and light chain 3B (LC3B)/COX IV were increased under Cd stress. Moreover, Cd exposure decreased the levels of mitochondrial biogenesis and fusion related factors and minichromosome maintenance protein 2 (MCM2), but increased the levels of mitochondrial fission, mitophagy, and cell aging related factors. However, the variations mentioned above caused by Cd were effectively ameliorated by Se co-treatment. In conclusion, Se might alleviate Cd-induced aging via regulating mitochondrial quality control in sheep livers.