Williams Frederick E, Sickelbaugh Traci J, Hassoun Ezdihar
Department of Pharmacology, College of Pharmacy, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA.
J Biochem Mol Toxicol. 2006;20(4):183-90. doi: 10.1002/jbt.20135.
The ability of ellagic acid (EA) to modulate dichloroacetic acid (DCA)-induced developmental toxicity and oxidative damage was examined in zebrafish embryos. Embryos were exposed to 20 mM EA administered concomitantly with 32 mM DCA at 4 hours postfertilization (hpf) and 20 h later. Embryos were observed through 144 hpf for developmental malformations, and production of superoxide anion (SA) and nitric oxide (NO) was determined in embryonic homogenates. DCA was shown to produce developmental abnormalities and significant levels of SA and NO in zebrafish embryos. EA exposure alleviated the developmental malformations observed in treated embryos and decreased the levels of SA and NO in those same embryos. Less than 10% of DCA + EA exposed embryos showed developmental malformations compared to 100% of embryos treated with DCA alone. Animals in this group that developed malformations were shown to have fewer defects than those treated with DCA only. Taken together, the results confirm the involvement of oxidative stress in the developmental toxicity of DCA in zebrafish embryos, and suggest possible protection against those effects with the use of antioxidants.
在斑马鱼胚胎中研究了鞣花酸(EA)调节二氯乙酸(DCA)诱导的发育毒性和氧化损伤的能力。在受精后4小时(hpf)和20小时后,将胚胎暴露于20 mM EA并同时给予32 mM DCA。在144 hpf观察胚胎的发育畸形情况,并测定胚胎匀浆中超氧阴离子(SA)和一氧化氮(NO)的产生。结果显示,DCA可导致斑马鱼胚胎出现发育异常以及显著水平的SA和NO。暴露于EA可减轻处理后胚胎中观察到的发育畸形,并降低这些胚胎中SA和NO的水平。与仅用DCA处理的100%胚胎相比,暴露于DCA + EA的胚胎中不到10%出现发育畸形。该组中出现畸形的动物显示出的缺陷比仅用DCA处理的动物少。综上所述,结果证实氧化应激参与了DCA对斑马鱼胚胎的发育毒性,并表明使用抗氧化剂可能对这些影响具有保护作用。