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Antioxidant Rescue of Selenomethionine-Induced Teratogenesis in Zebrafish Embryos

Arnold, M. C., Forte, J. E., Osterberg, J. S., Di Giulio, R. T.
Archives of environmental contamination and toxicology 2016 v.70 no.2 pp. 311-320
Danio rerio, abnormal development, acetylcysteine, antioxidants, coal, dose response, genes, glutamate-cysteine ligase, glutathione, glutathione transferase, mining, oxidative stress, protein subunits, runoff, selenates, selenites, selenium, selenomethionine, surface water, toxicity
Selenium (Se) is an essential micronutrient that can be found at toxic concentrations in surface waters contaminated by runoff from agriculture and coal mining. Zebrafish (Danio rerio) embryos were exposed to aqueous Se in the form of selenate, selenite, and L-selenomethionine (SeMet) in an attempt to determine if oxidative stress plays a role in selenium embryo toxicity. Selenate and selenite exposure did not induce embryo deformities (lordosis and craniofacial malformation). L-selenomethionine, however, induced significantly higher deformity rates at 100 µg/L compared with controls. SeMet exposure induced a dose-dependent increase in the catalytic subunit of glutamate-cysteine ligase (gclc) and reached an 11.7-fold increase at 100 µg/L. SeMet exposure also reduced concentrations of TGSH, RGSH, and the TGSH:GSSG ratio. Pretreatment with 100 µM N-acetylcysteine significantly reduced deformities in the zebrafish embryos secondarily treated with 400 µg/L SeMet from approximately 50–10 % as well as rescued all three of the significant glutathione level differences seen with SeMet alone. Selenite exposure induced a 6.6-fold increase in expression of the glutathione-S-transferase pi class 2 (gstp2) gene, which is involved in xenobiotic transformation and possibly oxidative stress. These results suggest that aqueous exposure to SeMet can induce significant embryonic teratogenesis in zebrafish that are at least partially attributed to oxidative stress.