A multi-omic approach to elucidate low-dose effects of xenobiotics in zebrafish (Danio rerio) larvae

Publication date: Available online 18 November 2016 Source:Aquatic Toxicology Author(s): Susie S.Y. Huang, Jonathan P. Benskin, Nik Veldhoen, Bharat Chandramouli, Heather Butler, Caren C. Helbing, John R. Cosgrove Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e. low-dose) effects, or differentiating between similar phenotypes induced by different chemicals. Inclusion of multi-omic analyses in studies investigating xenobiotic action provides improved characterization of biological response, thereby enhancing prediction of toxicological outcomes in whole animals in the absence of morphological effects. In the current study, we assessed perturbations in both the metabolome and transcriptome of zebrafish (Danio rerio; ZF) larvae exposed from 96–120h post fertilization to environmental concentrations of acetaminophen (APAP), diphenhydramine (DH), carbamazepine (CBZ), and fluoxetine (FLX); common pharmaceuticals with known mechanisms of action. Multi-omic responses were evaluated independently and integrated to identify molecular interactions and biological relevance of the responses. Results indicated chemical and dose-specific changes suggesting differences in the time scale of transcript abundance and metabolite production. Increased impact on the metabolome relative to the transcriptome ...
Source: Aquatic Toxicology - Category: Toxicology Source Type: research