New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway
Hearing loss is caused by many factors including ototoxic drug-induced hair cell damage. Ombuoside, an antioxidant isolated from Gynostemma pentaphyllum, has been suggested to serve as a new neuroprotective drug. However, the role of ombuoside in protecting inner ear hair cells from ototoxic drug-in...
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Elsevier
2024-10-01
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| author | Xingxing Wu Xixia Peng Yue Zhang Wanjun Peng Xiaochan Lu Tingting Deng Guohui Nie |
| author_facet | Xingxing Wu Xixia Peng Yue Zhang Wanjun Peng Xiaochan Lu Tingting Deng Guohui Nie |
| author_sort | Xingxing Wu |
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| description | Hearing loss is caused by many factors including ototoxic drug-induced hair cell damage. Ombuoside, an antioxidant isolated from Gynostemma pentaphyllum, has been suggested to serve as a new neuroprotective drug. However, the role of ombuoside in protecting inner ear hair cells from ototoxic drug-induced damage has not been investigated. Here, we demonstrated the protective potential of ombuoside in mitigating drug-induced ototoxicity in vivo and in vitro. We used cisplatin, a highly ototoxic anti-tumor drug, to induce hair cell damage. Our results showed that ombuoside significantly increased the survival of cisplatin-treated HEI-OC1 cells. Further mechanism research suggested that ombuoside protects HEI-OCI cells from cisplatin-induced apoptosis by reducing the cisplatin-induced upregulation of apoptosis-promoting proteins Bax, Bak, as well as apoptosis indicator proteins cytochrome C and cleaved-caspase-3, and the downregulation of apoptosis-inhibiting proteins Bcl-2. Ombuoside also protects the cells from the excessive ROS production and mitochondrial membrane depolarization triggered by cisplatin. These results demonstrated the potential for ombuoside in protecting hair cells from cisplatin by suppressing ROS generation and the mitochondrial apoptotic cascade. Ombuoside showed promise in protecting hair cells from cisplatin-induced apoptosis by suppressing ROS generation and the mitochondrial apoptotic cascade. Furthermore, ombuoside co-treatment in mouse cochlear explants and zebrafish lateral neuromasts rescued the decreased number and deformed morphology of hair cells resulting from cisplatin exposure. These findings further validated our conclusions and indicated that ombuoside is a potential protector against hearing loss caused by ototoxicity as a clinical side effect of cisplatin. |
| format | Article |
| id | doaj-art-98289ceca6dc4e23b8bb02ef80a20a67 |
| institution | OA Journals |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-98289ceca6dc4e23b8bb02ef80a20a672025-08-20T02:13:59ZengElsevierHeliyon2405-84402024-10-011020e3916610.1016/j.heliyon.2024.e39166New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathwayXingxing Wu0Xixia Peng1Yue Zhang2Wanjun Peng3Xiaochan Lu4Tingting Deng5Guohui Nie6Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518035, ChinaCenter for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, ChinaDepartment of Otolaryngology, Shaanxi Provincial People's Hospital, Xi'an, 710068, ChinaShenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518035, ChinaDepartment of Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen, 518036, ChinaShenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518035, ChinaShenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518035, China; Corresponding author.Hearing loss is caused by many factors including ototoxic drug-induced hair cell damage. Ombuoside, an antioxidant isolated from Gynostemma pentaphyllum, has been suggested to serve as a new neuroprotective drug. However, the role of ombuoside in protecting inner ear hair cells from ototoxic drug-induced damage has not been investigated. Here, we demonstrated the protective potential of ombuoside in mitigating drug-induced ototoxicity in vivo and in vitro. We used cisplatin, a highly ototoxic anti-tumor drug, to induce hair cell damage. Our results showed that ombuoside significantly increased the survival of cisplatin-treated HEI-OC1 cells. Further mechanism research suggested that ombuoside protects HEI-OCI cells from cisplatin-induced apoptosis by reducing the cisplatin-induced upregulation of apoptosis-promoting proteins Bax, Bak, as well as apoptosis indicator proteins cytochrome C and cleaved-caspase-3, and the downregulation of apoptosis-inhibiting proteins Bcl-2. Ombuoside also protects the cells from the excessive ROS production and mitochondrial membrane depolarization triggered by cisplatin. These results demonstrated the potential for ombuoside in protecting hair cells from cisplatin by suppressing ROS generation and the mitochondrial apoptotic cascade. Ombuoside showed promise in protecting hair cells from cisplatin-induced apoptosis by suppressing ROS generation and the mitochondrial apoptotic cascade. Furthermore, ombuoside co-treatment in mouse cochlear explants and zebrafish lateral neuromasts rescued the decreased number and deformed morphology of hair cells resulting from cisplatin exposure. These findings further validated our conclusions and indicated that ombuoside is a potential protector against hearing loss caused by ototoxicity as a clinical side effect of cisplatin.http://www.sciencedirect.com/science/article/pii/S2405844024151973OmbuosideCisplatinOtotoxicityReactive oxygen speciesApoptosis |
| spellingShingle | Xingxing Wu Xixia Peng Yue Zhang Wanjun Peng Xiaochan Lu Tingting Deng Guohui Nie New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway Heliyon Ombuoside Cisplatin Ototoxicity Reactive oxygen species Apoptosis |
| title | New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway |
| title_full | New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway |
| title_fullStr | New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway |
| title_full_unstemmed | New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway |
| title_short | New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway |
| title_sort | new application of ombuoside in protecting auditory cells from cisplatin induced ototoxicity via the apoptosis pathway |
| topic | Ombuoside Cisplatin Ototoxicity Reactive oxygen species Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024151973 |
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