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Styrene induced alterations in biomarkers of exposure and effects in the cochlea: mechanisms of hearing loss.

Authors
Chen-G; Chi-L; Kostyniak-PJ; Henderson-D
Source
Toxicol Sci 2007 Jul; 98(1):167-177
NIOSHTIC No.
20032118
Abstract
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, styreneinduced 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 styreneinduced 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 g/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 mitochondrialdependent pathway and death receptor-dependent pathway were involved in the styrene-induced cell death.
Keywords
Hearing-loss; Biomarkers; Styrenes; Auditory-system; Ototoxicity; Organic-chemicals; Cell-damage; Exposure-assessment; Exposure-levels; Dose-response
Contact
Guang-Di Chen, Center for Hearing and Deafness, SUNY at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214
CODEN
TOSCF2
CAS No.
100-42-5
Publication Date
20070701
Document Type
Journal Article
Email Address
gchen@buffalo.edu
Funding Type
Grant
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008113
Issue of Publication
1
ISSN
1096-6080
Source Name
Toxicological Sciences
State
NY
Performing Organization
State University of New York at Buffalo
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