Pravastatin Administration Alleviates Kanamycin-Induced Cochlear Injury and Hearing Loss

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 4524
• Main Authors: Lee, Chang Ho, Jeon, Jiwon, Lee, So Min, Kim, So Young
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.04.2022; MDPI
• Subjects: Aminoglycosides; Animals; Apoptosis; Autophagy; Brain stem; Caspase 3 - metabolism; Caspase-3; Cochlea; Cochlea - metabolism; Deafness - metabolism; Enzymes; Evoked Potentials, Auditory, Brain Stem; Ganglion cells; Hair; Hair cells; Hearing; Hearing loss; Hearing Loss - chemically induced; Hearing Loss - drug therapy; Hearing Loss - metabolism; Kanamycin; Kanamycin - pharmacology; Mammals; Ototoxicity; Outer hair cells; Oxidative stress; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Pravastatin; Pravastatin - pharmacology; Rats; Ribose; Spiral ganglion; Statins; Thresholds; Western blotting; aminoglycosides; hearing loss; ototoxicity; pravastatin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23094524

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.