Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats.
Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.
['Chun|Kyung-Ju|KJ|', 'Lee|Chang-Ho|CH|', 'Kim|Kyung-Woon|KW|', 'Lee|So-Min|SM|', 'Kim|So-Young|SY|0000-0002-7361-4930']
D059002:Androgen Receptor Antagonists D000818:Animals D000900:Anti-Bacterial Agents D001309:Auditory Threshold D003051:Cochlea D019363:Cytochrome P-450 CYP1A1 D065633:Cytochrome P-450 CYP1B1 D016057:Evoked Potentials, Auditory, Brain Stem D005485:Flutamide D015870:Gene Expression D006319:Hearing Loss, Sensorineural D007612:Kanamycin D026561:Low Density Lipoprotein Receptor-Related Protein-2 D008297:Male D008668:Metallothionein D020011:Protective Agents D012333:RNA, Messenger D051381:Rats D017207:Rats, Sprague-Dawley D014409:Tumor Necrosis Factor-alpha
hearing loss aminoglycosides metallothionein low-density lipoprotein receptor-related protein-2 receptors, androgen