Cisplatin-induced ototoxicity: From signaling network to therapeutic targets
Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis injury, spiral ganglion degeneration, and hair cell death. Over several decades, the research scope of cisplatin-induced ototoxicity has...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222014342 |
| _version_ | 1811299668814987264 |
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| author | Xilu Wang Yingying Zhou Dali Wang Yi Wang Zhaoyu Zhou Xiulan Ma Xiaofang Liu Yaodong Dong |
| author_facet | Xilu Wang Yingying Zhou Dali Wang Yi Wang Zhaoyu Zhou Xiulan Ma Xiaofang Liu Yaodong Dong |
| author_sort | Xilu Wang |
| collection | DOAJ |
| description | Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis injury, spiral ganglion degeneration, and hair cell death. Over several decades, the research scope of cisplatin-induced ototoxicity has expanded with the discovery of the molecular mechanism mediating inner ear cell death, highlighting the roles of reactive oxygen species and transport channels for cisplatin uptake into inner ear cells. Upon entering hair cells, cisplatin disrupts organelle metabolism, induces oxidative stress, and targets DNA to cause intracellular damage. Recent studies have also reported the role of inflammation in cisplatin-induced ototoxicity. In this article, we preform a narrative review of the latest reported molecular mechanisms of cisplatin-induced ototoxicity, from extracellular to intracellular. We build up a signaling network starting with cisplatin entering into the inner ear through the blood labyrinth barrier, disrupting cochlear endolymph homeostasis, and activating inflammatory responses of the outer hair cells. After entering the hair cells, cisplatin causes hair cell death via DNA damage, redox system imbalance, and mitochondrial and endoplasmic reticulum dysfunction, culminating in programmed cell death including apoptosis, necroptosis, autophagic death, pyroptosis, and ferroptosis. Based on the mentioned mechanisms, prominent therapeutic targets, such as channel-blocking drugs of cisplatin transporter, construction of cisplatin structural analogues, anti-inflammatory drugs, antioxidants, cell death inhibitors, and others, were collated. Considering the recent research efforts, we have analyzed the feasibility of the aforementioned therapeutic strategies and proposed our otoprotective approaches to overcome cisplatin-induced ototoxicity. |
| first_indexed | 2024-04-13T06:40:09Z |
| format | Article |
| id | doaj.art-628944c9040c4972a50514d67887774a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T06:40:09Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-628944c9040c4972a50514d67887774a2022-12-22T02:57:46ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-01-01157114045Cisplatin-induced ototoxicity: From signaling network to therapeutic targetsXilu Wang0Yingying Zhou1Dali Wang2Yi Wang3Zhaoyu Zhou4Xiulan Ma5Xiaofang Liu6Yaodong Dong7Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Obstetrics & gynecology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang, China; Corresponding authors.Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China; Corresponding authors.Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis injury, spiral ganglion degeneration, and hair cell death. Over several decades, the research scope of cisplatin-induced ototoxicity has expanded with the discovery of the molecular mechanism mediating inner ear cell death, highlighting the roles of reactive oxygen species and transport channels for cisplatin uptake into inner ear cells. Upon entering hair cells, cisplatin disrupts organelle metabolism, induces oxidative stress, and targets DNA to cause intracellular damage. Recent studies have also reported the role of inflammation in cisplatin-induced ototoxicity. In this article, we preform a narrative review of the latest reported molecular mechanisms of cisplatin-induced ototoxicity, from extracellular to intracellular. We build up a signaling network starting with cisplatin entering into the inner ear through the blood labyrinth barrier, disrupting cochlear endolymph homeostasis, and activating inflammatory responses of the outer hair cells. After entering the hair cells, cisplatin causes hair cell death via DNA damage, redox system imbalance, and mitochondrial and endoplasmic reticulum dysfunction, culminating in programmed cell death including apoptosis, necroptosis, autophagic death, pyroptosis, and ferroptosis. Based on the mentioned mechanisms, prominent therapeutic targets, such as channel-blocking drugs of cisplatin transporter, construction of cisplatin structural analogues, anti-inflammatory drugs, antioxidants, cell death inhibitors, and others, were collated. Considering the recent research efforts, we have analyzed the feasibility of the aforementioned therapeutic strategies and proposed our otoprotective approaches to overcome cisplatin-induced ototoxicity.http://www.sciencedirect.com/science/article/pii/S0753332222014342Cisplatin-induced ototoxicityInflammationOxidative stressProgrammed cell deathTherapeutic targets |
| spellingShingle | Xilu Wang Yingying Zhou Dali Wang Yi Wang Zhaoyu Zhou Xiulan Ma Xiaofang Liu Yaodong Dong Cisplatin-induced ototoxicity: From signaling network to therapeutic targets Biomedicine & Pharmacotherapy Cisplatin-induced ototoxicity Inflammation Oxidative stress Programmed cell death Therapeutic targets |
| title | Cisplatin-induced ototoxicity: From signaling network to therapeutic targets |
| title_full | Cisplatin-induced ototoxicity: From signaling network to therapeutic targets |
| title_fullStr | Cisplatin-induced ototoxicity: From signaling network to therapeutic targets |
| title_full_unstemmed | Cisplatin-induced ototoxicity: From signaling network to therapeutic targets |
| title_short | Cisplatin-induced ototoxicity: From signaling network to therapeutic targets |
| title_sort | cisplatin induced ototoxicity from signaling network to therapeutic targets |
| topic | Cisplatin-induced ototoxicity Inflammation Oxidative stress Programmed cell death Therapeutic targets |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222014342 |
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