Interactive effects of selenium on arsenic and cadmium induced toxicity in rainbow trout (Oncorhynchus mykiss)

The existing scientific literature suggests that selenium can modify arsenite or cadmium toxicity in fish; however, our current understanding of the biochemical pathways involved in such interactions is obtained predominantly from mammalian experimental systems, and the literature on aquatic organisms is sparse. To address this knowledge gap, the modulatory effects of selenium on cadmium or arsenite toxicity was investigated using a model freshwater fish, rainbow trout (Oncorhynchus mykiss). Interactions at the cellular level were investigated using trout hepatocytes in primary culture. Selenite and selenomethionine were used as the inorganic and organic chemical forms of selenium to understand the chemical species-dependent effects. Interactions at the organismal level were studied by feeding the fish with Artemia based diets supplemented with selenomethionine in combination with cadmium or arsenite for 30 days. At the cellular level, cadmium and arsenite disrupted redox homeostasis which was alleviated by low-moderate doses of selenite and selenomethionine (< 25 µM). Further analysis revealed that selenite antagonized arsenite-induced oxidative stress by augmenting enzymatic antioxidants, whereas selenomethionine upregulated the GSH-dependent non-enzymatic antioxidative pathway. At the organismal level, supplementing the diet with only cadmium (40 µg/g diet) or arsenite (80 µg/g diet) increased the tissue level deposition of the respective elements and caused oxidative stress in the liver. However, medium dose (10 µg/g diet) of selenomethionine reduced cadmium accumulation in the liver and alleviated oxidative stress. In contrast, supplementation of diet with selenomethionine (both at low and high levels) in combination with arsenite resulted in higher degree of oxidative stress relative to the fish treated with arsenite alone. Furthermore, fish co-treated with arsenite and selenomethionine accumulated significantly higher levels of arsenic in liver, kidney and muscle relative to fish treated with arsenite alone. Similarly, the synchrotron-based X-ray fluorescence imaging also revealed a dose-dependent increase in the co-localization of arsenic and selenium in the brain of fish co-treated with dietary arsenite and selenomethionine, whereas no arsenic deposition in the brain was recorded in fish treated with dietary arsenite alone. Overall, the results indicated that selenium at moderate doses could antagonize cadmium-induced oxidative stress; however, selenomethionine can interact metabolically with arsenite at systemic level and increase its toxicity in fish