Selenium triggers Nrf2-mediated protection against cadmium-induced chicken hepatocyte autophagy and apoptosis

Cadmium (Cd) is a ubiquitously distributed trace metal and environmental pollutant that is highly toxic to liver. Selenium (Se) may provide chemoprotection against Cd-induced cytotoxicity by augmenting the cellular antioxidant capacity. However, the mechanism of Se chemoprotection against Cd-induced hepatotoxicity is unclear. The present study evaluated the ameliorative properties of Se against Cd-induced cytotoxicity in hepatocytes. Primary cells were exposed to 5 mu M Cd and/or 1 mu M Se for 24 h. Cellular morphology and function, antioxidant status, activation of Nrf2 pathway, autophagy and apoptosis were determined. These results indicated that Se ameliorated the cytotoxicity of Cd by recovering hepatocyte morphology and function, inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) production, reducing intracellular LDH release, autophagy and apoptosis, and increasing the major antioxidative activities (Total antioxidant capacity (T-AOC) and superoxide dismutase (SOD). In summary, Cd is a hepatotoxin that causes hepatocytes damage by inducing oxidative stress, excessive autophagy and apoptosis as a mechanism of toxicity. Moreover, Se supplement ameliorated these effects by enhancing antioxidant systems, decreasing excessive autophagy and apoptosis. These results suggested that Se triggers Nrf2-mediated protection as the mechanism of Se chemoprotection against Cd-induced autophagy and apoptosis.