Zebrafish based assays for the assessment of cardiac, visual and gut function — potential safety screens for early drug discovery

摘要: Abstract Introduction Safety pharmacology is integral to the non-clinical safety assessment of new chemical entities prior first administration humans. The zebrafish a well established model organism that has been shown be relevant study human diseases. potential role in was evaluated using reference compounds three models assessing cardiac, visual and intestinal function. Methods: Compound toxicity determine non toxic concentration blinded set 16 compounds. In cardiac assay, larvae at 3 days post fertilisation (d.p.f.) were exposed for 3 h before measurement atrial ventricular rates. To investigate function, optomotor response assessed 8 d.p.f. following 5 day compound exposure. function number gut contractions measured 7 d.p.f. after 1 h Finally, uptake determined 9 measure absorbed by larvae. Results: Seven out nine produced an expected effect statistically significant functions assays. contraction six ten showed also result whilst two displayed anticipated but non-significant effects. method used larval tissue concentrations allowed identification false negatives when poorly into zebrafish. Discussion: Overall, results generated assays demonstrated good correlation between effects data available from other vivo or known clinical adverse These suggest have predict drug supports their possible early novel