Dose and chemical species-specific effects of selenium against arsenite toxicity in cultured hepatocytes of rainbow trout (Oncorhynchus mykiss)
The present study evaluated the mechanistic underpinnings of the interactive effects of selenium (Se), both inorganic (selenite) and organic (selenomethionine (SeMet)), against arsenite (As-III) cytotoxicity using rainbow trout (Oncorhynchus mykiss) hepatocytes in primary culture. Arsenite is known to induce cytotoxic effects by disrupting cellular redox homeostasis. In contrast, Se is essential for the maintenance of cellular anti-oxidative machinery, but when present above a threshold concentration, can also induce reactive oxygen species (ROS) generation and cause oxidative damage. In this study, hepatocytes were exposed to 100 μM arsenite independently or in combination with selenite or SeMet (5–40 μM) for 24 h. Exposure to arsenite alone reduced cell viability by inducing intracellular ROS generation, which also corresponded with a concomitant decrease in cellular thiol (GSH : GSSG) ratio and the activities of enzymatic antioxidants (GPx and SOD). Both selenite and SeMet were found to ameliorate the arsenite-induced loss of cell viability and thiol balance significantly, but only at low-intermediate exposure levels (5–20 μM), with selenite being more effective than SeMet. Further analyses of cellular antioxidative pathways, using specific pharmacological treatments, revealed that selenite and SeMet mediate their protective effects against arsenite toxicity via different mechanisms. Selenite ameliorates arsenite-induced oxidative stress primarily by augmenting enzymatic antioxidants (especially SOD), whereas SeMet elicits its protective response essentially by upregulating the non-enzymatic antioxidative pathway that involves GSH. Overall, our study demonstrated that the antagonistic interactions of arsenite and Se at the cellular level are influenced by the exposure dose as well as the chemical speciation of Se.
- This article is part of the themed collection: Metals in marine biochemistry