The effect of statins on aminoglycoside-induced ototoxicity is controversial. This study aimed to explore the role of pravastatin (PV) in kanamycin-induced hearing loss in rats. Adult rats were intraperitoneally treated with 20 mg/kg/day of kanamycin (KM) for 10 days. In the PV- and PV + KM-treated rats, 25 mg/kg/day of PV was intraperitoneally administered for 5 days. The auditory brainstem response (ABR) thresholds were measured before and after drug treatment using a smartEP system at 4, 8, 16, and 32 kHz. Cochlear changes in poly ADP-ribose (PAR) polymerase (PARP), PAR, and caspase 3 were estimated using Western blotting. PV administration did not increase the ABR thresholds. The KM-treated rats showed elevated ABR thresholds at 4, 8, 16, and 32 kHz. The PV + KM-treated rats demonstrated lower ABR thresholds than the KM-treated rats at 4, 8, and 16 kHz. The cochlear outer hair cells and spiral ganglion cells were relatively preserved in the PV + KM-treated rats when compared with that in the KM-treated rats. The cochlear expression levels of PARP, PAR, and caspase 3 were higher in the KM-treated rats. The PV + KM-treated rats showed lower levels of PARP, PAR, and caspase 3 than the KM-treated rats. PV protected cochleae from KM-induced hearing loss in rats. The regulation of autophagy and apoptosis mediated the otoprotective effects of PV.
Keywords: aminoglycosides; hearing loss; ototoxicity; pravastatin.