Selenium prevent cadmium-induced hepatotoxicity through modulation of endoplasmic reticulum-resident selenoproteins and attenuation of endoplasmic reticulum stress

Cadmium (Cd), a heavy metal contaminant, exists in humans and animals throughout life and closely associate with severe hepatotoxicity. Selenium (Se) has been recognized as an effective chemoprotectant of Cd, but the underlying mechanisms remain unclear. The objective of the present study is to illustrate the antagonistic effect of Se against Cd-induced hepatotoxicity. Primary hepatocytes were cultured in the presence of 5 mu M Cd, 1 mu M Se and the mixture of 1 mu M Se and 5 mu M Cd for 24 h. Cell viability and morphology, antioxidant status, endoplasmic reticulum (ER) stress response and selenotranscriptome were assessed. It was observed that Se treatment dramatically alleviated Cd-induced hepatocytes death and morphological change. Simultaneously, Se mitigated Cd-induced oxidative stress by reducing ROS production, increasing reduced glutathione (GSH) level and increasing selenoenzyme (glutathione peroxidase, GPX) activity. Cd induced hepatotoxicity via disordering ER-resident selenoproteins transcription and triggering ER stress and unfolded protein response. Supplementary Se evidently relieved hepatocytes injury via modulating ER-resident selenoproteins transcription to inhibit ER stress. Collectively, our findings showed a potential protection of Se against Cd-induced hepatotoxicity via suppressing ER stress response. (C) 2020 Elsevier Ltd. All rights reserved.