The antioxidant effect of compounds is regularly evaluated by in vitro assays that do not have the capability to predict in vivo protective activity or to determine their underlying mechanisms of action. The aim of this study was to develop an experimental system to evaluate the in vivo protective effects of different antioxidant compounds, based on the zebrafish embryo test. Zebrafish embryos were exposed to tert-butyl hydroperoxide (tBOOH), tetrachlorohydroquinone (TCHQ) and lipopolysaccharides from Escherichia coli (LPS), chemicals that are known inducers of oxidative stress in zebrafish. The developmental toxic effects (lethality or dysmorphogenesis) induced by these chemicals were modulated with n-acetyl l-cysteine and Nω-nitro l-arginine methyl ester hydrochloride, dimethyl maleate and dl-buthionine sulfoximine in order to validate the oxidant mechanism of oxidative stress inducers. The oxidant effects of tBOOH, TCHQ, and LPS were confirmed by the determination of significant differences in the comparison between the concentration–response curves of the oxidative stress inducers and of the modulators of antioxidant status. This concept was also applied to the study of the effects of well-known antioxidants, such as vitamin E, quercetin, and lipoic acid. Our results confirm the zebrafish model as an in vivo useful tool to test the protective effects of antioxidant compounds.

中文翻译：

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抗氧化剂对氧化剂诱导的斑马鱼发育毒性的调节和保护作用。

化合物的抗氧化作用是通过不具有预测体内保护活性或确定其潜在作用机制的能力的体外测定法定期评估的。这项研究的目的是基于斑马鱼胚胎试验，开发一种评估不同抗氧化剂化合物在体内保护作用的实验系统。斑马鱼的胚胎暴露于叔丁基过氧化氢（tBOOH），四氯氢醌（TCHQ）和来自大肠杆菌（LPS）的脂多糖，这些化学物质是斑马鱼氧化应激的已知诱因。通过这些化学物质所引起的发育毒性作用（致死性或畸形发生）与被调制ñ -乙酰基升-半胱氨酸和Ñ ω硝基为了验证氧化应激诱导剂的氧化机理，使用了1-精氨酸甲酯盐酸盐，马来酸二甲酯和dl-丁硫氨酸磺酰亚胺。通过确定氧化应激诱导剂和抗氧化剂状态调节剂的浓度-响应曲线之间比较的显着差异，可以证实tBOOH，TCHQ和LPS的氧化作用。该概念还用于研究著名的抗氧化剂，例如维生素E，槲皮素和硫辛酸的作用。我们的结果证实了斑马鱼模型是测试抗氧化剂的保护作用的体内有用工具。