| Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway. | |
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MedLine Citation:
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PMID: 21519324 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aminoglycoside ototoxicity is a common cause of drug-induced hearing loss. Toxicity is dose related, but some patients may still develop hearing loss even under safe dosage. Apart for genetic idiosyncrasy, indirect evidences imply that ischemia may increase the aminoglycoside ototoxic sensitivity because common clinical situations associated with cochlear ischemia such as noise, sepsis, and shock are known to augment the development of aminoglycoside ototoxicity. At present, a direct interaction of cochlear ischemia and aminoglycoside ototoxicity is still lacking. This study demonstrated a direct evidence of increased gentamicin (GM) ototoxic sensitivity in chronic guinea pig models of transient cochlear ischemia. No permanent auditory changes were observed after a single dose of GM (125 mg/kg) or after transient cochlear ischemia for 30 min. Persistent and significant auditory threshold shift was detected when GM was given after transient cochlear ischemia. Cochlear hair cells and spiral ganglion neurons are the major regions affected. Apoptosis contributes to hair cell death during acute interaction of ischemia and GM ototoxicity. Increased apoptotic cell death was also depicted when GM crossreacted with hypoxia in vitro, using cochlear cell lines. Generation of reactive oxygen species, loss of mitochondrial membrane potential, calcium release, and caspase-dependent apoptotic cell death were shown during the interaction of hypoxia and GM ototoxicity in vitro. This synergistic ototoxicity may be critical to aminoglycoside-induced hearing loss in clinical scenarios. The results should improve our understanding of the interacting mechanism and potential preventive strategy to aminoglycoside ototoxicity.Laboratory Investigation advance online publication, 25 April 2011; doi:10.1038/labinvest.2011.69. |
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Authors:
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Chia-Der Lin; Ming-Ching Kao; Ming-Hsui Tsai; Chih-Ho Lai; I-Hua Wei; Mang-Hung Tsai; Chih-Hsin Tang; Cheng-Wen Lin; Chuan-Jen Hsu; Ching-Yuang Lin |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-25 |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: - ISSN: 1530-0307 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan [2] Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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