Figure 8.

Differential patterns of analog protection from gentamicin. Zebrafish were either pre-treated with the OPC of analog for 1 h, then co-treated with analog and gentamicin for 30 min (“pre-co” condition), co-treated with analog and gentamicin without a pretreatment period (“co” condition) or post-treated with analog for 5.5 h following gentamicin removal (“post” condition). All treatments used 200 μM gentamicin. Examples are shown for analogs that represent each pattern of protection. (A) Analog BA-1 was only protective when administered in the “pre-co” or “co” conditions suggesting that protection occurs via aminoglycoside uptake block. (B,C) Analogs BA-6 and BA-7 significantly protected hair cells in all three conditions, suggesting an intracellular mechanism of protection in addition to aminoglycoside uptake block. (D) Analog BA-16 is not protective of any treatment paradigm. Hair cells were assessed via DASPEI. Data are presented normalized to untreated controls, which are not shown but represent 100% hair cell survival. Data were analyzed via one-way ANOVA, ****p < 0.0001, **p < 0.01 (as compared to gentamicin-only controls), N = 7–12, bars are + SEM. Refer to Supplementary Table S1 for statistics.