Pravastatin Administration Alleviates Kanamycin-Induced Cochlear Injury and Hearing Loss

被引:6
|
作者
Lee, Chang Ho [1 ]
Jeon, Jiwon [1 ]
Lee, So Min [1 ]
Kim, So Young [1 ]
机构
[1] CHA Univ, CHA Bundang Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Seongnam 13496, South Korea
基金
新加坡国家研究基金会;
关键词
hearing loss; pravastatin; aminoglycosides; ototoxicity; POLY(ADP-RIBOSE) POLYMERASE-1; PROTECTS; AIF; MECHANISMS; SCREEN; CELLS;
D O I
10.3390/ijms23094524
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:9
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