Dale K, Rasinger J D, Thorstensen K L, Penglase S, Ellingsen S
National Institute of Nutrition and Seafood Research (NIFES), PO Box 2029, NO-5817 Bergen, Norway.
National Institute of Nutrition and Seafood Research (NIFES), PO Box 2029, NO-5817 Bergen, Norway.
Food Chem Toxicol. 2017 Mar;101:84-93. doi: 10.1016/j.fct.2017.01.004. Epub 2017 Jan 6.
The aim of this study was to investigate if vitamin E (α-TOC) modulates the developmental toxicity of the pesticide endosulfan (ESF), using a modified zebrafish embryotoxicity test (ZET). Zebrafish (Danio rerio) embryos were exposed from 6 to 72 h post fertilization (hpf) to either ESF (0.1-50 mg/L) or α-TOC (0.01-3 mM) alone or in combination. The effects of these exposures on embryonic morphology, larval behavior and antioxidant gene expression were analyzed. Phenotypic analysis at 48 hpf showed that ESF led to a dose-dependent increase in embryonic deformities, including axis malformations, pericardial edema and reduced pigmentation. Co-exposure of ESF with α-TOC (1-3 mM) significantly (p < 0.05) reduced ESF-induced embryonic malformations. Exposure to solely α-TOC did not affect rates of survival or malformations. Behavior studies showed that ESF caused hyperactivity at 5 days post fertilization, indicating a developmental neurotoxic effect. The ESF-induced hyperactivity was ameliorated by α-TOC. Elevated ESF concentrations caused down-regulation of the antioxidant genes cuzn-sod, gpx1a and cat, suggesting that ESF promoted oxidative stress in the embryos. α-TOC did not prevent the ESF-induced dysregulation of these genes. These results demonstrate that α-TOC protects against phenotypic and behavioral effects caused by ESF but did not rescue ESF-induced aberrations in antioxidant gene expression.
本研究的目的是使用改良的斑马鱼胚胎毒性试验(ZET),研究维生素E(α-生育酚)是否能调节农药硫丹(ESF)的发育毒性。斑马鱼(Danio rerio)胚胎在受精后6至72小时(hpf)暴露于单独或组合的ESF(0.1 - 50mg/L)或α-生育酚(0.01 - 3mM)。分析了这些暴露对胚胎形态、幼体行为和抗氧化基因表达的影响。48 hpf时的表型分析表明,ESF导致胚胎畸形呈剂量依赖性增加,包括轴畸形、心包水肿和色素沉着减少。ESF与α-生育酚(1 - 3mM)共同暴露显著(p < 0.05)降低了ESF诱导的胚胎畸形。仅暴露于α-生育酚不影响存活率或畸形率。行为研究表明,ESF在受精后5天引起多动,表明存在发育神经毒性作用。α-生育酚改善了ESF诱导的多动。ESF浓度升高导致抗氧化基因cuzn-sod、gpx1a和cat的下调,表明ESF促进了胚胎中的氧化应激。α-生育酚并未阻止ESF诱导的这些基因的失调。这些结果表明,α-生育酚可保护免受ESF引起的表型和行为影响,但不能挽救ESF诱导的抗氧化基因表达异常。