Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss
Background: To investigate the pathophysiology of age-related hearing loss (ARHL) and the mechanism of resveratrol (RSV) in prevention and treatment of ARHL.Methods: C57BL/6 mice of different ages were used in this study. Auditory brainstem response (ABR) was performed to assess hearing and identify...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.910308/full |
| _version_ | 1828803581555245056 |
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| author | Zeyin Yang Zeyin Yang Yan Zhang Shuling Yang Yongqing Ding Yan Qu |
| author_facet | Zeyin Yang Zeyin Yang Yan Zhang Shuling Yang Yongqing Ding Yan Qu |
| author_sort | Zeyin Yang |
| collection | DOAJ |
| description | Background: To investigate the pathophysiology of age-related hearing loss (ARHL) and the mechanism of resveratrol (RSV) in prevention and treatment of ARHL.Methods: C57BL/6 mice of different ages were used in this study. Auditory brainstem response (ABR) was performed to assess hearing and identify abnormalities. Surface preparation and hair cell-specific marker Myo VIIa were employed to evaluated cochlear hair cell losses. Scanning electron microscopy (SEM) was to observe the microstructure of the organ of Corti (OC). The expression of related proteins in the RIPK1/RIPK3/MLKL pathway in cochlear tissue was detected by immunofluorescence.Results: In old mice (15 months), the ABR threshold increased significantly compared with the young mice. After 50 mg/kg RSV intervention, the hearing threshold of the old mice was significantly reduced at 8 kHz and 12 kHz as well as click. 100 mg/kg RSV led to a statistically significant reduction in hearing threshold only at clicks, whereas 300 mg/kg RSV showed no difference at all frequencies tested. In terms of cochlear hair cell loss, the damage of OHC and IHC was severe in old mice, but the damage was evidently reduced in RSV 50 mg/kg group. Notably, in the RSV 300 mg/kg group, the loss and disorientation of both the OHCs and IHCs were aggravated. Under SEM, a large number of OHCs were lost in the old group, but increased significantly in the RSV 50 mg/kg group, and even the OHCs were more seriously damaged in the RSV 300 mg/kg group. Furthermore, immunofluorescence showed that 50 mg/kg RSV significantly reduced the expression of RIPK3, RIPK1, and MLKL in the cochlea during aging, especially in necroptosis-sensitive regions OCs and SGN.Conclusion: Low-dose RSV inhibited RIPK3-mediated necroptosis in aging cochlea and delayed the onset of ARHL, which was a promising therapeutic strategy for ARHL. |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T07:24:48Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-71e216b53c664bd7aa26c6d57ff3edaa2022-12-22T00:33:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.910308910308Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing LossZeyin Yang0Zeyin Yang1Yan Zhang2Shuling Yang3Yongqing Ding4Yan Qu5Department of Otolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaENT & HN Surgery Department, Shijiazhuang People’s Hospital, Shijiazhuang, ChinaDepartment of Otolaryngology, Tangshan People’s Hospital, Tangshan, ChinaAnimal Laboratory, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Otolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaBackground: To investigate the pathophysiology of age-related hearing loss (ARHL) and the mechanism of resveratrol (RSV) in prevention and treatment of ARHL.Methods: C57BL/6 mice of different ages were used in this study. Auditory brainstem response (ABR) was performed to assess hearing and identify abnormalities. Surface preparation and hair cell-specific marker Myo VIIa were employed to evaluated cochlear hair cell losses. Scanning electron microscopy (SEM) was to observe the microstructure of the organ of Corti (OC). The expression of related proteins in the RIPK1/RIPK3/MLKL pathway in cochlear tissue was detected by immunofluorescence.Results: In old mice (15 months), the ABR threshold increased significantly compared with the young mice. After 50 mg/kg RSV intervention, the hearing threshold of the old mice was significantly reduced at 8 kHz and 12 kHz as well as click. 100 mg/kg RSV led to a statistically significant reduction in hearing threshold only at clicks, whereas 300 mg/kg RSV showed no difference at all frequencies tested. In terms of cochlear hair cell loss, the damage of OHC and IHC was severe in old mice, but the damage was evidently reduced in RSV 50 mg/kg group. Notably, in the RSV 300 mg/kg group, the loss and disorientation of both the OHCs and IHCs were aggravated. Under SEM, a large number of OHCs were lost in the old group, but increased significantly in the RSV 50 mg/kg group, and even the OHCs were more seriously damaged in the RSV 300 mg/kg group. Furthermore, immunofluorescence showed that 50 mg/kg RSV significantly reduced the expression of RIPK3, RIPK1, and MLKL in the cochlea during aging, especially in necroptosis-sensitive regions OCs and SGN.Conclusion: Low-dose RSV inhibited RIPK3-mediated necroptosis in aging cochlea and delayed the onset of ARHL, which was a promising therapeutic strategy for ARHL.https://www.frontiersin.org/articles/10.3389/fphar.2022.910308/fullage-related hearing losspresbycusisresveratrolnecroptosisripk3aging cochlea |
| spellingShingle | Zeyin Yang Zeyin Yang Yan Zhang Shuling Yang Yongqing Ding Yan Qu Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss Frontiers in Pharmacology age-related hearing loss presbycusis resveratrol necroptosis ripk3 aging cochlea |
| title | Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss |
| title_full | Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss |
| title_fullStr | Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss |
| title_full_unstemmed | Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss |
| title_short | Low-Dose Resveratrol Inhibits RIPK3-Mediated Necroptosis and Delays the Onset of Age-Related Hearing Loss |
| title_sort | low dose resveratrol inhibits ripk3 mediated necroptosis and delays the onset of age related hearing loss |
| topic | age-related hearing loss presbycusis resveratrol necroptosis ripk3 aging cochlea |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.910308/full |
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