Due to the small size and optically clear body of larval fish, the zebrafish lateral line is a powerful system for identifying and evaluating drugs that damage or protect hair cells. The zebrafish lateral line is morphologically and physiologically similar to the inner ear hair cells. Owing to their location on the body surface, damage to hair cells can be rapidly assessed. In addition, because of the rapidity with which the experiments can be performed using zebrafish and the large population available, zebrafish are particularly valuable for thoroughly testing and modulating dose-response relationships.
In one example, libraries of 88 anti-cancer drugs were screened to evaluate the damage of hair cells on the zebrafish lateral line. The screen identified 13 drugs that caused hair cell damage. We further evaluated the effects of common combinations of anti-cancer drugs and identified evidence of synergistic hair cell toxicity.
Conversely, 18 supplement drugs and 80-kinase inhibitors were screened to evaluate their protective effects on the hair cells of the zebrafish lateral line; this allowed identification of three supplements and some kinase inhibitors with protective activity.
The results of our study indicate that screening drugs using zebrafish potentially allows determination of drugs with ototoxic effects/protective effects for the inner ear.
