Document Detail


Mefloquine damage vestibular hair cells in organotypic cultures.
MedLine Citation:
PMID:  20859773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mefloquine is an effective and widely used anti-malarial drug; however, some clinical reports suggest that it can cause dizziness, balance, and vestibular disturbances. To determine if mefloquine might be toxic to the vestibular system, we applied mefloquine to organotypic cultures of the macula of the utricle from postnatal day 3 rats. The macula of the utricle was micro-dissected out as a flat surface preparation and cultured with 10, 50, 100, or 200 μM mefloquine for 24 h. Specimens were stained with TRITC-conjugated phalloidin to label the actin in hair cell stereocilia and TO-PRO-3 to visualize cell nuclei. Some utricles were also labeled with fluorogenic caspase-3, -8, or -9 indicators to evaluate the mechanism of programmed cell death. Mefloquine treatment caused a dose-dependent loss of utricular hair cells. Treatment with 10 μM caused a slight reduction, 50 μM caused a significant reduction, and 200 μM destroyed nearly all the hair cells. Hair cell nuclei in mefloquine-treated utricles were condensed and fragmented, morphological features of apoptosis. Mefloquine-treated utricles were positive for the extrinsic initiator caspase-8 and intrinsic initiator caspase-9 and downstream executioner caspase-3. These results indicate that mefloquine can induce significant hair cell degeneration in the postnatal rat utricle and that mefloquine-induced hair cell death is initiated by both caspase-8 and caspase-9.
Authors:
Dongzhen Yu; Dalian Ding; Haiyan Jiang; Daniel Stolzberg; Richard Salvi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-22
Journal Detail:
Title:  Neurotoxicity research     Volume:  20     ISSN:  1476-3524     ISO Abbreviation:  Neurotox Res     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-05-09     Completed Date:  2011-09-23     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acoustic Maculae / drug effects*,  metabolism,  pathology*
Animals
Caspases / metabolism
Cell Death / drug effects
Dose-Response Relationship, Drug
Hair Cells, Vestibular / metabolism,  pathology*
Mefloquine / toxicity*
Nerve Degeneration / chemically induced*,  pathology
Organ Culture Techniques
Rats
Rats, Inbred F344
Grant Support
ID/Acronym/Agency:
R01 DC006630/DC/NIDCD NIH HHS; R01 DC006630-05/DC/NIDCD NIH HHS; R01DC006630/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
EC 3.4.22.-/Caspases; TML814419R/Mefloquine
Comments/Corrections

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