Cadmium treatment induces oxidative damage and apoptosis in vitro skeletal muscle cells

Abstract

Cadmium is a prevalent environmental contaminant, and current research indicates that exposure to cadmium is a significant risk factor contributing to the increased incidence of sarcopenia. However, the precise mechanisms by which cadmium exposure leads to skeletal muscle damage remain to be fully elucidated. Utilizing an in vitro culture model of mouse C2C12 myoblasts, this study exposed cells to 0, 2, 4, and 8 μmol/L cadmium chloride for 24 hours to evaluate the cellular damage and explore the potential mechanisms. Our present data of this study demonstrate that cadmium treatment results in a reduction of C2C12 cell viability, an increased release of lactate dehydrogenase, and an imbalance in the oxidative-antioxidant system characterized by an excessive accumulation of reactive oxygen species, elevated malondialdehyde production, and decreased superoxide dismutase activity. Additionally, there is an upregulation of nuclear factor-erythroid 2-related factor 2, heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and glutamate-cysteine ligase catalytic subunit protein expression, along with a downregulation of superoxide dismutase 1 protein expression. Furthermore, cadmium exposure mediates an increase in cysteinyl aspartate specific proteinase-dependent apoptosis via the mitochondrial pathway, as indicated by an increased apoptosis rate, elevated Bcl-2 associated X protein and cysteinyl aspartate specific proteinase 3 protein expression, and a decreased expression of B-cell lymphoma-2 protein. Our findings elucidate the mechanisms of cadmium-induced cytotoxic damage in skeletal muscle cells from the perspectives of oxidative injury and apoptosis, thereby providing a theoretical basis for the prevention and treatment of cadmium toxicity.