{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T03:03:00Z","timestamp":1771297380491,"version":"3.50.1"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271176"],"award-info":[{"award-number":["82271176"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cisplatin causes hearing loss in at least 60% of chemotherapy patients, leading to impairments in the patient\u2019s life quality. Spiral ganglion neurons (SGNs) and hair cells (HCs) are the main cell types affected by cisplatin accumulation in the inner ear. Fasudil is an FDA-approved drug and has been reported to exert neuroprotective effects in previous research. However, whether fasudil possesses protective effects in cisplatin-induced SGN and HC damage and the potential mechanisms remain unknown. In this study, we investigated whether fasudil has a protective effect on cisplatin-induced damage to inner ear SGNs and HCs. We first observed the effect of different concentrations of fasudil on cisplatin-induced cell loss of SGNs and HCs. We also studied the effects of fasudil on cisplatin-induced apoptosis of SGNs and HCs and detected the mitochondrial reactive oxygen species (ROS) level. Furthermore, we investigated the mechanisms of fasudil in protecting the SGNs and HCs from cisplatin- induced cells apoptosis. We found that fasudil treatment significantly ameliorated SGNs and HCs loss and attenuated cell apoptosis after cisplatin exposure. Moreover, fasudil attenuated the cisplatin-induced ROS generation in SGN- and HC-explants culture. Further mechanistic studies revealed that fasudil regulated the ROCK\/PTEN\/AKT signaling pathway in SGN- and HC-explants after cisplatin exposure. This study indicates that fasudil might be a novel therapeutic target for preventing cisplatin-induced SGNs and HCs damage.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf030","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T16:12:51Z","timestamp":1741191171000},"source":"Crossref","is-referenced-by-count":2,"title":["Fasudil protects spiral ganglion neurons and hair cells against cisplatin-induced apoptosis by inhibiting reactive oxygen species accumulation and regulating the ROCK\/PTEN\/AKT signaling pathway"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4061-2078","authenticated-orcid":false,"given":"Peng","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Shengli Oilfield Central Hospital , No. 38 Jinan Road, Dongying District, Dongying 257034 ,","place":["China"]},{"name":"Department of Otolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University , No. 4 Duanxing West Road, Huaiyin District, Jinan 250022 ,","place":["China"]},{"name":"Shandong Institute of Otorhinolaryngology , No. 4 Duanxing West Road, Huaiyin District, Jinan 250022 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Shengli Oilfield Central Hospital , No. 38 Jinan Road, Dongying District, Dongying 257034 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University , No. 4 Duanxing West Road, Huaiyin District, Jinan 250022 ,","place":["China"]},{"name":"Shandong Institute of Otorhinolaryngology , No. 4 Duanxing West Road, Huaiyin District, Jinan 250022 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shusheng","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University , No. 95 Yong'an Road, Xicheng District, Beijing 10050 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Shengli Oilfield Central Hospital , No. 38 Jinan Road, Dongying District, Dongying 257034 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaomin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University , No. 4 Duanxing West Road, Huaiyin District, Jinan 250022 ,","place":["China"]},{"name":"Shandong Institute of 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