Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress
Background and PurposeCisplatin is a widely used chemotherapy drug for the treatment of solid tumours, but its clinical benefit is often limited by ototoxicity, leading to irreversible sensorineural hearing loss. However, there is a lack of effective strategies to prevent hearing loss caused by cisp...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1641174/full |
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| author | Zhifeng Chen Zhifeng Chen Zhifeng Chen Ting Xie Chenyu Chen Chenyu Chen Chenyu Chen Tingting Lin Xiaobo Wu Xiaobo Wu Yuqing Chen Yuqing Chen Yanchun Lin Yanchun Lin Xiaoyang Luo Xiaoyang Luo Chaojun Zeng Chaojun Zeng Chaojun Zeng Chang Lin Chang Lin Chang Lin |
| author_facet | Zhifeng Chen Zhifeng Chen Zhifeng Chen Ting Xie Chenyu Chen Chenyu Chen Chenyu Chen Tingting Lin Xiaobo Wu Xiaobo Wu Yuqing Chen Yuqing Chen Yanchun Lin Yanchun Lin Xiaoyang Luo Xiaoyang Luo Chaojun Zeng Chaojun Zeng Chaojun Zeng Chang Lin Chang Lin Chang Lin |
| author_sort | Zhifeng Chen |
| collection | DOAJ |
| description | Background and PurposeCisplatin is a widely used chemotherapy drug for the treatment of solid tumours, but its clinical benefit is often limited by ototoxicity, leading to irreversible sensorineural hearing loss. However, there is a lack of effective strategies to prevent hearing loss caused by cisplatin in adults, while sodium thiosulfate is approved by the Food and Drug Administration in the United States for only use at the pediatric level. Sarsasapogenin, a natural compound of the Anemarrhena asphodelides, has antioxidant and neuroprotective properties, which suggest that it may attenuate the ototoxicity induced by cisplatin. The aim of this study is to evaluate the otoprotective effects of sarsasapogenin and its underlying mechanism as a potential therapeutic intervention for the prevention of ototoxicity induced by cisplatin.MethodsCell viability was assessed by CCK-8 and cell apoptosis was assessed by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial dysfunction were quantified by immunofluorescence. In addition, expression of the molecules involved in apoptosis and ferroptosis was analyzed by qRT-PCR and Western blot. In vivo auditory function was evaluated by auditory brainstem response testing, and the survival of hair cells in the cochlea was quantified by immunolabeling with myosin-VIIa.ResultsSarsasapogenin significantly alleviated cisplatin-induced oxidative stress and restored mitochondrial function in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. Furthermore, sarsasapogenin effectively protected against cisplatin-induced sensorineural hearing loss and hair cell degeneration in vivo. Mechanistically, the protective effects of sarsasapogenin were primarily mediated through the inhibition of apoptosis and ferroptosis, both in vitro and in vivo.ConclusionThis study provides compelling evidence for the otoprotective effects of sarsasapogenin, suggesting its potential as a therapeutic intervention to prevent cisplatin-induced hearing loss. |
| format | Article |
| id | doaj-art-e0569ab7171a481bb5967bace9862531 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-e0569ab7171a481bb5967bace98625312025-08-20T03:36:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.16411741641174Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stressZhifeng Chen0Zhifeng Chen1Zhifeng Chen2Ting Xie3Chenyu Chen4Chenyu Chen5Chenyu Chen6Tingting Lin7Xiaobo Wu8Xiaobo Wu9Yuqing Chen10Yuqing Chen11Yanchun Lin12Yanchun Lin13Xiaoyang Luo14Xiaoyang Luo15Chaojun Zeng16Chaojun Zeng17Chaojun Zeng18Chang Lin19Chang Lin20Chang Lin21Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Institute of Otolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Hepatopancreatobiliary Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaNHC Key Laboratory of Hearing Medicine Research, Eye & ENT Hospital, Fudan University, Shanghai, ChinaUniversity of Science and Technology of China, Hefei, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otolaryngology, Affiliated Hospital of Putian University, Putian, ChinaPutian Institute of Otolaryngology, Affiliated Hospital of Putian University, Putian, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Otorhinolaryngology-Head and Neck Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Institute of Otolaryngology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaBackground and PurposeCisplatin is a widely used chemotherapy drug for the treatment of solid tumours, but its clinical benefit is often limited by ototoxicity, leading to irreversible sensorineural hearing loss. However, there is a lack of effective strategies to prevent hearing loss caused by cisplatin in adults, while sodium thiosulfate is approved by the Food and Drug Administration in the United States for only use at the pediatric level. Sarsasapogenin, a natural compound of the Anemarrhena asphodelides, has antioxidant and neuroprotective properties, which suggest that it may attenuate the ototoxicity induced by cisplatin. The aim of this study is to evaluate the otoprotective effects of sarsasapogenin and its underlying mechanism as a potential therapeutic intervention for the prevention of ototoxicity induced by cisplatin.MethodsCell viability was assessed by CCK-8 and cell apoptosis was assessed by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial dysfunction were quantified by immunofluorescence. In addition, expression of the molecules involved in apoptosis and ferroptosis was analyzed by qRT-PCR and Western blot. In vivo auditory function was evaluated by auditory brainstem response testing, and the survival of hair cells in the cochlea was quantified by immunolabeling with myosin-VIIa.ResultsSarsasapogenin significantly alleviated cisplatin-induced oxidative stress and restored mitochondrial function in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. Furthermore, sarsasapogenin effectively protected against cisplatin-induced sensorineural hearing loss and hair cell degeneration in vivo. Mechanistically, the protective effects of sarsasapogenin were primarily mediated through the inhibition of apoptosis and ferroptosis, both in vitro and in vivo.ConclusionThis study provides compelling evidence for the otoprotective effects of sarsasapogenin, suggesting its potential as a therapeutic intervention to prevent cisplatin-induced hearing loss.https://www.frontiersin.org/articles/10.3389/fphar.2025.1641174/fullsarsasapogeninototoxicitycisplatinapoptosisferroptosisoxidative stress |
| spellingShingle | Zhifeng Chen Zhifeng Chen Zhifeng Chen Ting Xie Chenyu Chen Chenyu Chen Chenyu Chen Tingting Lin Xiaobo Wu Xiaobo Wu Yuqing Chen Yuqing Chen Yanchun Lin Yanchun Lin Xiaoyang Luo Xiaoyang Luo Chaojun Zeng Chaojun Zeng Chaojun Zeng Chang Lin Chang Lin Chang Lin Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress Frontiers in Pharmacology sarsasapogenin ototoxicity cisplatin apoptosis ferroptosis oxidative stress |
| title | Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress |
| title_full | Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress |
| title_fullStr | Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress |
| title_full_unstemmed | Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress |
| title_short | Sarsasapogenin protects hair cells from cisplatin-induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress |
| title_sort | sarsasapogenin protects hair cells from cisplatin induced ototoxicity by attenuating apoptosis and ferroptosis via alleviating oxidative stress |
| topic | sarsasapogenin ototoxicity cisplatin apoptosis ferroptosis oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1641174/full |
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