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. 2016 Feb;70(2):311-20.
doi: 10.1007/s00244-015-0235-7.

Antioxidant Rescue of Selenomethionine-Induced Teratogenesis in Zebrafish Embryos

M C Arnold  1 , J E Forte, J S Osterberg, R T Di Giulio
Affiliations

Antioxidant Rescue of Selenomethionine-Induced Teratogenesis in Zebrafish Embryos

M C Arnold et al. Arch Environ Contam Toxicol. 2016 Feb.

Erratum in

Abstract

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.

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Figures

Fig. 1
Fig. 1
Percentage of 48 hpf zebrafish embryos dead (a) and deformed (b) after treatment with L-selenomethionine (SeMet). Error bars are standard error and asterisks represent significant differences from controls (P<0.05)
Fig. 2
Fig. 2
Zebrafish (Danio rerio) embryos A. control (48 hpf) B. 100 μg/L L-selenomethionine (48 hpf) exposed embryo with craniofacial and tail deformities with pericardial edema C. 100 μg/L L-selenomethionine (48 hpf) exposed embryo with significant deformity D. 30 μg/L selenite (72 hpf) exposed embryo with lordosis and pericardial edema
Fig. 3
Fig. 3
Dose response curve for deformities induced in zebrafish embryos by L-selenomethionine exposure. Dotted lines represent the 95% confidence interval. Calculated EC50 = 84 μg/L
Fig. 4
Fig. 4
Percentage of 48 hpf zebrafish embryos dead (a) and deformed (b) after treatment with various concentrations of selenate and selenite. Error bars represent standard error.
Fig. 5
Fig. 5
Fold change in gene expression for embryos treated with control, selenate, or selenite aqueous exposures. Asterisk indicates significance (p ≤ 0.05) from respective control. Error bars represent standard error
Fig. 6
Fig. 6
Fold change in gene expression in embryos treated with control or L-selenomethionine (SeMet) aqueous exposures. Asterisk indicates significance (p ≤ 0.05) from respective control. Error bars represent standard error
Fig. 7
Fig. 7
Percentage of 72 hpf zebrafish embryos dead (a) and deformed (b) after treatment with 100 uM N-acetylcysteine (NAC) and/or 400 μg/L L-selenomethionine (SeMet). Error bars are standard error. Asterisk represents significant difference from all other treatments (p<0.001)
Fig. 8
Fig. 8
Glutathione levels in zebrafish embryos at 72 hpf (a) including total glutathione (TGSH), reduced glutathione (RGSH), and oxidized glutathione (GSSG). The ratio of TGSH:GSSG is plotted in (b). Error bars are standard error. Asterisks represent significant difference from all other treatments within glutathione type
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