Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro
Aminoglycoside-induced ototoxicity can have a major impact on patients’ quality of life and social development problems. Oxidative stress affects normal physiologic functions and has been implicated in aminoglycoside-induced inner ear injury. Excessive accumulation of reactive oxygen species (ROS) d...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00702/full |
| _version_ | 1819020499165904896 |
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| author | Hezhou Han Yaodong Dong Xiulan Ma |
| author_facet | Hezhou Han Yaodong Dong Xiulan Ma |
| author_sort | Hezhou Han |
| collection | DOAJ |
| description | Aminoglycoside-induced ototoxicity can have a major impact on patients’ quality of life and social development problems. Oxidative stress affects normal physiologic functions and has been implicated in aminoglycoside-induced inner ear injury. Excessive accumulation of reactive oxygen species (ROS) damages DNA, lipids, and proteins in cells and induces their apoptosis. Dihydromyricetin (DHM) is a natural flavonol with a wide range of health benefits including anti-inflammatory, antitumor, and antioxidant effects; however, its effects and mechanism of action in auditory hair cells are not well understood. The present study investigated the antioxidant mechanism and anti-ototoxic potential of DHM using House Ear Institute-Organ of Corti (HEI-OC)1 auditory cells and cochlear explant cultures prepared from Kunming mice. We used gentamicin to establish aminoglycoside-induced ototoxicity models. Histological and physiological analyses were carried out to determine DHM’s pharmacological effects on gentamicin-induced ototoxicity. Results showed DHM contributes to protecting cells from apoptotic cell death by inhibiting ROS accumulation. Western blotting and quantitative RT-PCR analyses revealed that DHM exerted its otoprotective effects by up-regulating levels of peroxisome proliferator activated receptor γ-coactivator (PGC)-1α and Sirtuin (SIRT)3. And the role of PGC-1α and SIRT3 in the protective effects of DHM was evaluated by pharmacologic inhibition of these factors using SR-18292 and 3-(1H-1,2,3-triazol-4-yl) pyridine, respectively, which indicated DHM’s protective effect was dependent on activation of the PGC-1α/SIRT3 signaling. Our study is the first report to identify DHM as a potential otoprotective drug and provides a basis for the prevention and treatment of hearing loss caused by aminoglycoside antibiotic-induced oxidative damage to auditory hair cells. |
| first_indexed | 2024-12-21T03:52:11Z |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T03:52:11Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c4dc7f24b4544cce8e0c3812a1be6cb42022-12-21T19:16:57ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00702558909Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitroHezhou HanYaodong DongXiulan MaAminoglycoside-induced ototoxicity can have a major impact on patients’ quality of life and social development problems. Oxidative stress affects normal physiologic functions and has been implicated in aminoglycoside-induced inner ear injury. Excessive accumulation of reactive oxygen species (ROS) damages DNA, lipids, and proteins in cells and induces their apoptosis. Dihydromyricetin (DHM) is a natural flavonol with a wide range of health benefits including anti-inflammatory, antitumor, and antioxidant effects; however, its effects and mechanism of action in auditory hair cells are not well understood. The present study investigated the antioxidant mechanism and anti-ototoxic potential of DHM using House Ear Institute-Organ of Corti (HEI-OC)1 auditory cells and cochlear explant cultures prepared from Kunming mice. We used gentamicin to establish aminoglycoside-induced ototoxicity models. Histological and physiological analyses were carried out to determine DHM’s pharmacological effects on gentamicin-induced ototoxicity. Results showed DHM contributes to protecting cells from apoptotic cell death by inhibiting ROS accumulation. Western blotting and quantitative RT-PCR analyses revealed that DHM exerted its otoprotective effects by up-regulating levels of peroxisome proliferator activated receptor γ-coactivator (PGC)-1α and Sirtuin (SIRT)3. And the role of PGC-1α and SIRT3 in the protective effects of DHM was evaluated by pharmacologic inhibition of these factors using SR-18292 and 3-(1H-1,2,3-triazol-4-yl) pyridine, respectively, which indicated DHM’s protective effect was dependent on activation of the PGC-1α/SIRT3 signaling. Our study is the first report to identify DHM as a potential otoprotective drug and provides a basis for the prevention and treatment of hearing loss caused by aminoglycoside antibiotic-induced oxidative damage to auditory hair cells.https://www.frontiersin.org/article/10.3389/fcell.2020.00702/fulldihydromyricetinaminoglycosidesototoxicityPGC-1αsirtuin 3reactive oxygen species |
| spellingShingle | Hezhou Han Yaodong Dong Xiulan Ma Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro Frontiers in Cell and Developmental Biology dihydromyricetin aminoglycosides ototoxicity PGC-1α sirtuin 3 reactive oxygen species |
| title | Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro |
| title_full | Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro |
| title_fullStr | Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro |
| title_full_unstemmed | Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro |
| title_short | Dihydromyricetin Protects Against Gentamicin-Induced Ototoxicity via PGC-1α/SIRT3 Signaling in vitro |
| title_sort | dihydromyricetin protects against gentamicin induced ototoxicity via pgc 1α sirt3 signaling in vitro |
| topic | dihydromyricetin aminoglycosides ototoxicity PGC-1α sirtuin 3 reactive oxygen species |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00702/full |
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