Document Detail

Styrene induced alterations in biomarkers of exposure and effects in the cochlea: mechanisms of hearing loss.
MedLine Citation:
PMID:  17420221     Owner:  NLM     Status:  MEDLINE    
It is known that styrene is ototoxic and causes cochlear damage starting from the middle turn. However, the cellular mechanism underlying styrene ototoxicity is still unclear. In this study, rats were exposed to styrene by gavage at different doses once a day for varying periods. Styrene levels in the cochlear tissues, styrene-induced permanent hearing loss, cochlear disruptions, and cell death pathways were determined. Styrene concentration in the cochlea varied along with the basilar membrane with the lowest level in the basal turn being consistent with the lowest styrene-induced threshold shift and hair cell loss in this region. After 3 weeks of exposure (5 days per week), a dose-dependent permanent hearing loss and a hair cell loss, especially in the midfrequency region, were observed. The styrene exposure at a dose of 200 mg/kg, which induced a blood level of 6.0 +/- 1.0 microg/g, caused an average of 4.4 +/- 0.5% OHC (outer hair cell) loss and 2-5 dB threshold shift in the cochlear region of 20-70% from the apex. A significant OHC loss was not observed until 7 days of exposure at a dose of 800 mg/kg. Deiters cells appeared to be the most vulnerable target of styrene. When condensed nuclei were observed in Deiters cells after a few days of styrene exposure (800 mg/kg), other cells were still intact. Apoptotic cell death appeared to be the main cell death pathway in the cochlea after styrene exposure. In the styrene-induced apoptotic OHCs, histochemical staining detected activated caspases-9 and 8, indicating that both mitochondrial-dependent pathway and death receptor-dependent pathway were involved in the styrene-induced cell death.
Guang-Di Chen; Lai-Har Chi; Paul J Kostyniak; Donald Henderson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-04-09
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  98     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-15     Completed Date:  2007-09-06     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167-77     Citation Subset:  IM    
Center for Hearing and Deafness, SUNY at Buffalo, Buffalo, New York, USA.
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MeSH Terms
Actins / metabolism
Administration, Inhalation
Apoptosis / drug effects
Biological Markers
Caspases / metabolism
Cell Death / drug effects
Cell Nucleus / drug effects,  pathology,  ultrastructure
Chromatography, Gas
Cochlea / drug effects*,  pathology
Hair Cells, Auditory / drug effects,  pathology
Hearing Loss / chemically induced*,  pathology
Intubation, Gastrointestinal
Perilymph / metabolism
Rats, Long-Evans
Rats, Sprague-Dawley
Solid Phase Extraction
Styrene / blood,  pharmacokinetics,  toxicity*
Grant Support
Reg. No./Substance:
0/Actins; 0/Biological Markers; 100-42-5/Styrene; EC 3.4.22.-/Caspases

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