Effect of ketamine on gene expression in zebrafish embryos

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. Used as an anesthetic, potential neurotoxic and cardiotoxic effects of ketamine in animal models have been reported. The underlying mechanisms of ketamine-induced toxicity are not clear. The zebrafish is an ideal model for toxicity assays because of its predictive capability in chemical testing, which compares well with that of mammalian models. To gain insight into potential mechanisms of ketamine effects, we performed real-time quantitative polymerase chain reaction-based gene expression array analyses. Gene expression analysis was conducted for multiple genes (a total of 84) related to 10 major signaling pathways including the transforming growth factor β (TGFβ), Wingless and Int-1 (Wnt), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), Janus kinase/signal transducers and activators of transcription (JAK/STAT), p53, Notch, Hedgehog, peroxisome proliferator-activated receptor (PPAR), oxidative stress, and hypoxia pathways. Our results show that ketamine altered the expression of specific genes related to hypoxia, p53, Wnt, Notch, TGFβ, PPAR, and oxidative stress pathways. Thus, we can further focus on these specific pathways to elucidate the mechanisms by which ketamine elicits a toxic response.