PMID- 35127378
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220208
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jan
TI  - Astaxanthine attenuates cisplatin ototoxicity in vitro and protects against 
      cisplatin-induced hearing loss in vivo.
PG  - 167-181
LID - 10.1016/j.apsb.2021.07.002 [doi]
AB  - 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 between 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 mitochondrial 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 results 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 
      promoting cell survival. Our study demonstrates that AST is a candidate 
      therapeutic agent for CIHL.
CI  - (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Nan, Benyu
AU  - Nan B
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Zhongshan Hospital, 
      Fudan University, Shanghai 200030, China.
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Wenzhou Medical 
      University, Affiliated Hospital 2, Wenzhou 325000, China.
FAU - Zhao, Zirui
AU  - Zhao Z
AD  - Department of Otolaryngology, Yueyang Hospital of Integrated Traditional Chinese 
      and Western Medicine, Shanghai University of Traditional Chinese Medicine, 
      Shanghai 200437, China.
FAU - Jiang, Kanglun
AU  - Jiang K
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Zhongshan Hospital, 
      Fudan University, Shanghai 200030, China.
FAU - Gu, Xi
AU  - Gu X
AD  - Department of Otolaryngology, the First Affiliated Hospital of Fujian Medical 
      University, Fuzhou 350005, China.
FAU - Li, Huawei
AU  - Li H
AD  - 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.
AD  - Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
AD  - NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, 
      China.
AD  - The Institutes of Brain Science and the Collaborative Innovation Center for Brain 
      Science, Fudan University, Shanghai 200032, China.
FAU - Huang, Xinsheng
AU  - Huang X
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Zhongshan Hospital, 
      Fudan University, Shanghai 200030, China.
LA  - eng
PT  - Journal Article
DEP - 20210710
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC8800030
OTO - NOTNLM
OT  - Apoptosis
OT  - Astaxanthine
OT  - Cisplatin
OT  - Hearing loss
OT  - Mitochondrial
OT  - Ototoxicity
OT  - Reactive oxygen species
EDAT- 2022/02/08 06:00
MHDA- 2022/02/08 06:01
PMCR- 2021/07/10
CRDT- 2022/02/07 05:33
PHST- 2021/03/11 00:00 [received]
PHST- 2021/06/03 00:00 [revised]
PHST- 2021/06/16 00:00 [accepted]
PHST- 2022/02/07 05:33 [entrez]
PHST- 2022/02/08 06:00 [pubmed]
PHST- 2022/02/08 06:01 [medline]
PHST- 2021/07/10 00:00 [pmc-release]
AID - S2211-3835(21)00251-3 [pii]
AID - 10.1016/j.apsb.2021.07.002 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2022 Jan;12(1):167-181. doi: 10.1016/j.apsb.2021.07.002. Epub 
      2021 Jul 10.