Contributions from extracellular sources of adenosine to the ethanol toxicity in zebrafish larvae

The effects of ethanol exposure on extracellular adenosine sources in zebrafish were evaluated. In the acute treatment, the embryos were exposed to 2% ethanol on day 1 post-fertilization (dpf). In the chronic treatment, the exposure was continued for 2h/day up to 6 dpf. Ecto-5'-nucleotidase activity was assessed by colorimetric method and gene expression determined by RT-qPCR in 7 dpf zebrafish. Body length, ocular distance and surface area of the eyes were registered in animals acutely exposed to ethanol and pretreated with AOPCP (5-500 nM), an ecto-5'-nucleotidase inhibitor, or dipyridamole (10-100 μM), a blocker of nucleoside transport. Both ethanol exposures promoted increased ecto-5'-nucleotidase activity, impaired locomotion and morphology. Ecto-5'-nucleotidase expression was not affected. AOPCP promoted mild prevention of morphological defects caused by acute treatment, while dipyridamole worsened these defects. Early ethanol exposure altered adenosinergic tonus, especially through nucleoside transporters, contributing to morphological defects produced by ethanol in zebrafish.