Astaxanthine(AST)has important biological activities including antioxidant and anti-inflammatory effects that could alleviate neurological and heart diseases,but its role in the prevention of cisplatin-induced hearing loss(CIHL)is not yet well understood.In our study,a steady interaction be-tween AST and the E3 ligase adapter Kelch-like ECH-associated protein 1,a predominant repressor of nuclear factor erythroid 2-related factor 2(NRF2),was performed and tested via computer molecular docking and dynamics.AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathway using quantitative PCR and Western blotting.The levels of reactive oxygen species(ROS)and mitochon-drial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction.Moreover,AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting.Finally,AST combined with poloxamer was injected into the middle ear through the tympanum,and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice.Our re-sults suggest that AST reduced ROS overexpression,mitochondrial dysfunction,and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants,finally promot-ing cell survival.Our study demonstrates that AST is a candidate therapeutic agent for CIHL.

Benyu Nan;Zirui Zhao;Kanglun Jiang;Xi Gu;Huawei Li;Xinsheng Huang

Department of Otorhinolaryngology-Head and Neck Surgery,Zhongshan Hospital,Fudan University,Shanghai 200030,China;Department of Otorhinolaryngology-Head and Neck Surgery,Wenzhou Medical University,Affiliated Hospital 2,Wenzhou 325000,China;Department of Otolaryngology,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Department of Otolaryngology,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China;ENT Institute and Department of Otorhinolaryngology,Eye & ENT Hospital,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Fudan University,Shanghai 200031,China;Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China;NHC Key Laboratory of Hearing Medicine(Fudan University),Shanghai 200031,China;The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science,Fudan University,Shanghai 200032,China

药学学报（英文版）

[1]Benyu Nan;Zirui Zhao;Kanglun Jiang;Xi Gu;Huawei Li;Xinsheng Huang-.Astaxanthine attenuates cisplatin ototoxicity in vitro and protects against cisplatin-induced hearing loss in vivo)[J].药学学报（英文版）,2022(01):167-181

Astaxanthine,CIHL,tympanum

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