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 administere...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5307 |
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| author | Kyung-Ju Chun Chang-Ho Lee Kyung-Woon Kim So-Min Lee So-Young Kim |
| author_facet | Kyung-Ju Chun Chang-Ho Lee Kyung-Woon Kim So-Min Lee So-Young Kim |
| author_sort | Kyung-Ju Chun |
| collection | DOAJ |
| description | 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 <i>p</i> < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all <i>p</i> < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all <i>p</i> < 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. |
| first_indexed | 2024-03-10T11:17:57Z |
| format | Article |
| id | doaj.art-42cfb03d82964234876e07be1abdd4c5 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:17:57Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-42cfb03d82964234876e07be1abdd4c52023-11-21T20:16:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210530710.3390/ijms22105307Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in RatsKyung-Ju Chun0Chang-Ho Lee1Kyung-Woon Kim2So-Min Lee3So-Young Kim4Department of Otorhinolaryngology-Head & Neck Surgery, CHA University College of Medicine, Seongnam 13496, KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, CHA University College of Medicine, Seongnam 13496, KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, CHA University College of Medicine, Seongnam 13496, KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, CHA University College of Medicine, Seongnam 13496, KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, CHA University College of Medicine, Seongnam 13496, KoreaMegalin 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 <i>p</i> < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all <i>p</i> < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all <i>p</i> < 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.https://www.mdpi.com/1422-0067/22/10/5307receptors, androgenaminoglycosideshearing losslow-density lipoprotein receptor-related protein-2metallothionein |
| spellingShingle | Kyung-Ju Chun Chang-Ho Lee Kyung-Woon Kim So-Min Lee So-Young Kim Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats International Journal of Molecular Sciences receptors, androgen aminoglycosides hearing loss low-density lipoprotein receptor-related protein-2 metallothionein |
| title | Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats |
| title_full | Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats |
| title_fullStr | Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats |
| title_full_unstemmed | Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats |
| title_short | Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats |
| title_sort | effects of androgen receptor inhibition on kanamycin induced hearing loss in rats |
| topic | receptors, androgen aminoglycosides hearing loss low-density lipoprotein receptor-related protein-2 metallothionein |
| url | https://www.mdpi.com/1422-0067/22/10/5307 |
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