Dose-dependent effect of aminoglycoside treatments on hair cells of transgenic ET4 zebrafish

In human, aminoglycoside treatment disrupts inner ear hair cells leading to hearing and balance disorders. It is well known that the mammalian inner ear does not present regenerative capacity while the fish hair cells located in the inner ear and in the lateral system have an high capacity of regeneration. The hair cells of the lateral line system of zebrafish resemble for their morphology and molecular aspect those present in the hu-man inner ear. For this reason the zebrafish lateral line offers several advantages that make it a powerful ani-mal model for studying hair cells regeneration and ototoxicity drug screening. In the present study we exam-ined the dose-dependent effects of two aminoglycosides, neomycin and gentamicin, in the hair cells of the lateral line in the ET4 transgenic line. The fishes were treated with the aminoglycosides for 24h at different dose levels. Immediately after treatment the morphological observation and the counts of the neuromast hair cells have been made on L1 (First Lateral Neuromast located in the trunk) and T1 (First Terminal Neuromast located in the fin). The results show that neomycin and gentamicin have different effect on the hair cells death at the same concentration, showing also different toxicity in L1 neuromast and T1 neuromast. The toxicity observed in the hair cells of T1 neuromast was less than in L1 neuromast, with particular reference to the gentamicin treatment. The morpho-functional evidence of this data provides a strong support to the use of the zebrafish as a pre-clinical indicator of drug-induced ototoxicity.