Selenium alleviates cadmium-induced oxidative stress, endoplasmic reticulum stress, and apoptosis in L8824 cells.

Cadmium (Cd) is a toxic pollutant in industrial production that induces organ damage and apoptosis, While, selenium (Se) has the biological function of antagonizing Cd toxicity. Hence, to gain further insight into the protective mechanisms of selenium against Cd-induced damage in Ctenopharyngodon idella liver (L8824) cells, L8824 were exposed to 5 μM, 15 μM, 25 μM cadmium chloride for 24 h after pre-incubation with 25 μM sodium selenite for 9 h. Cell proliferation and morphological changes, the levels of reactive oxygen species (ROS) and antioxidant enzyme activity, mitochondrial membrane potential (MMP), endoplasmic reticulum stress (ERS)-related pathway genes expression, intracellular calcium levels and apoptosis were assessed to explore the protective effect of selenium in Cd-induced L8824 cell damage. The results showed that Cd caused decreased cell viability, ROS accumulation, reduced activity of antioxidant enzymes (SOD, CAT GPx and T-AOC) and apoptosis in L8824 cells. The incubation of Se prominently ameliorated cell proliferation, activated the Keap1-Nrf2 pathway, and restored antioxidant enzyme activity. Furthermore, the expression of grp78, perk, eif-2α, atf4, chop bax, jnk, caspase-3 and caspase-9 was significantly upregulated after Cd exposure, while the expression of bcl-2 was significantly downregulated. Se supplementation alleviated Cd-induced ERS and apoptosis. Moreover, Cd-induced elevation of intracellular Ca2+ levels were alleviated by dantrolene and 2-APB, suggesting that intracellular calcium disorders were caused by Ca2+ released by RyR and IP3R-mediated ER. The results of this study suggested that Cd could induce oxidative stress, ERS, mitochondrial damage and evoke apoptosis, whereas Se had protective effects in preventing Cd induced damage by inhibiting ERS, maintaining intracellular calcium homeostasis, enhancing the antioxidant capacity of L8824 cells and downregulating the Keap1/Nrf2 pathway.