Berbamine analogs reduce aminoglycoside uptake by hair cells. (A) Twelve of the analogs significantly reduced uptake of gentamicin conjugated with Texas Red (GTTR), as did berbamine. Zebrafish were pretreated with the optimally protective analog concentration (or with 25 μM berbamine, Kruger et al., 2016) for 1 h followed by a co-treatment with 50 μM GTTR for 18 min. Dimethylsulfoxide (DMSO) and high calcium are negative and positive controls, respectively. (B) Fluorescence intensity quantification using the OPC of analog. The intensity was measured in arbitrary units and the data were normalized by subtracting the background fluorescence. Data were analyzed via one-way ANOVA, F(17,101) = 38.71, ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, asterisks denote significantly different from vehicle controls, N = 4–8 for most compounds, except for N = 2 for compounds BA-1 and BA-5 and N = 15 for berbamine, bars are ± SEM. (C) Linear regression was conducted for analogs that protect hair cells from gentamicin to identify a relationship between analog potency and uptake (y = −0.0203x + 0.9162). The Pearson correlation coefficient of 0.2268 denotes no significant relationship. Berbamine data are replotted from Kruger et al. (2016).
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