Abstract
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.
Highlights
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are products of cellular metabolism, which play a dual role in beneficial and deleterious effects over different organs [1]
The aim of the present work was to design an experimental system based on the ZF embryo test, which could be the basis for the study of in vivo protective effects of chemicals with antioxidant activity against oxidant-induced developmental toxicity in ZF embryos
The ZF embryo has been established as the basis for the study of the modulative and protective effects of antioxidant compounds in oxidant induced developmental toxicity in ZF
Summary
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are products of cellular metabolism, which play a dual role in beneficial and deleterious effects over different organs [1]. Aerobic organisms have antioxidant defenses to protect cells from oxidative damage. The consequences of OS can be very variable depending on the reactive species implicated, the subcellular structure where they are generated, the organs or tissues implicated in the effect, the genetic characteristics of the organism or developmental stage, among other factors. It is a phenomenon which has been related to different processes (aging, cancer, diabetes, cardiovascular and neurodegenerative diseases, etc.) as it can damage and inhibit the normal function of lipids, proteins, and DNA [4]
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