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

• Published in: Environmental pollution (1987) 2020-05, Vol.260, p.113873-113873, Article 113873
• Main Authors: Zhang, Cong, Ge, Jing, Lv, Meiwei, Zhang, Qi, Talukder, Milton, Li, Jin-Long
• Format: Article
• Language: English
• Subjects: Animals; Cadmium; Cadmium - toxicity; Chemical and Drug Induced Liver Injury; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress; Hepatotoxicity; Oxidative Stress - drug effects; Selenium; Selenium - pharmacology; Selenoprotein; Selenoproteins - biosynthesis
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2019.113873

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 chemo-protectant 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 μM Cd, 1 μM Se and the mixture of 1 μM Se and 5 μM 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. Se prevents Cd-induced hepatotoxicity through modulation of ER-resident selenoproteins and attenuation of ER Stress. [Display omitted] •Cd could cause hepatocytes morphological change and death.•Cd disrupts ER-resident selenoproteins and triggers UPR and ER stress.•Se inhibits Cd-induced ER stress and hepatocytes death.•Se regulates ER-resident selenoproteins to alleviate Cd-induced ER Stress.