Toxicogenomics and Drug Monitoring

Biography

Biography: Eva Lima Castro Oliveira

Abstract

The zebrafish is considered a promising alternative test model for developmental toxicity testing. The normal vertebrate development requires appropriate amounts of Retinoic acid (RA). All-trans retinoic acid (atRA) and 9-cis retinoic acid (9cRA) are potent metabolites of Vitamin A and operate by affecting gene expression through the retinoic acid metabolic pathway. atRA or 9cRA can bind to retinoic acid receptors (RARs) and the 9cRA isomer bind to retinoid X receptors (RXRs) with more affinity. The exogenous application of retinoid isomers to zebrafish is considered to have deleterious effects of varying magnitudes through fish developmental stages. In this study, we report both phenotypic and transcriptomic effects of zebrafish eleutheroembryos exposed RA isomers for 24h and 72h. Nevertheless at sub-lethal concentrations the both RA isomers showed a differential regulation for 3623 features (2-Fold, p<0.01). The transcriptomic analyses reveal profiles describing different patterns, which allow individualizing the action of both isomers. Nevertheless the differential gene expression of both isomers is stable during the period of exposure. We concluded that the 9cRA response appears to be deactivated upon time, perhaps through its intracellular degradation and/or isomerization, and that the presence of any compound masking or anyway interfering with their effective levels may cause harmful effects to developing vertebrate embryos. Our data suggests that Retinoids effects on early embryonic zebrafish development are stage-specific and is related in particular to the neuronal system behavior. Also, the regulation of the Vitamin-A dietary intake may be a special concern for future studies on the development of zebrafish eleuteroembryos.