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. 2018 Apr 2;215(4):1187–1203. doi: 10.1084/jem.20172246

Figure 3.

Figure 3.

Locally delivered kenpaullone (ken) protects against cisplatin (CIS)-induced HC loss and hearing loss in adult mice and rats in vivo. (A) Experimental design. One ear of each FVB WT mouse at P28 was trans-tympanically injected with compound (250 µM ken in 0.5% DMSO in a volume of 5 µl), and the other ear was injected with 0.5% DMSO only, in a random order. 2 h later, the mice were injected i.p. with CIS at 30 mg/kg body weight, which was expected to damage the OHCs in both ears equally. ABR thresholds were recorded for each ear before or at D7 or D14 after ken or DMSO treatment with CIS administration, and cochlear histology was examined at D14. All analysis was performed in a double-blinded manner. (B) ABR threshold shifts in ken-treated ears (red) versus DMSO-treated control ears (black) of 11 mice at D14. Results are presented as the mean ± SEM. P = 0.0221 at 16 kHz, and P = 0.0215 at 32 kHz. (C) Representative confocal images of cochleae at the 32-kHz region double stained with phalloidin with an antibody to the HC marker myosin 7a (Myo7a) at D14. Bar, 20 µM. (D) Comparison of the percentage of OHC survival in the 32-kHz region in ken- and DMSO-treated ears after CIS administration in all 11 mice in four cohorts. Each line links the two cochleae of one mouse. P = 0.0028 by the paired two-tailed Student’s t test. (E and F) The left ear of each Wistar rat (body weight 306–354 g) was trans-tympanically injected with compound (310 µM ken in 0.5% DMSO; red curve) or carrier (0.5% DMSO; black curve) in a volume of 30 µl. 1 h later, the rat was injected i.p. with CIS at 13 mg/kg body weight. ABR thresholds were recorded 1 d before and 4 d after CIS administration. Error bars: SEM. N, number of rats tested in each group (two cohorts). As controls, four rats were injected trans-tympanically with 310 µM ken only, without CIS treatment (blue curve). All analysis was performed in a double-blinded manner. Note that significant differences in protection (28.5, 41.7, 36.2, and 41.5 dB at 4, 8, 16, and 22 kHz, respectively) were detected between ken/CIS and DMSO/CIS rats, whereas no significant differences were detected between ken/CIS and ken alone rats at these four frequencies. *, P < 0.05 and **, P < 0.01 by the unpaired two-tailed Student’s t test.