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ToxSci Advance Access originally published online on April 9, 2007
Toxicological Sciences 2007 98(1):167-177; doi:10.1093/toxsci/kfm078
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Styrene Induced Alterations in Biomarkers of Exposure and Effects in the Cochlea: Mechanisms of Hearing Loss

Guang-Di Chen*,1, Lai-Har Chi{dagger}, Paul J. Kostyniak{dagger} and Donald Henderson*

* Center for Hearing and Deafness, and {dagger} Toxicology Research Center, SUNY at Buffalo, Buffalo, New York

1 To whom correspondence should be addressed. Fax: (716) 829-2980. E-mail: gchen7{at}buffalo.edu.

Received January 25, 2007; accepted April 2, 2007


  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, 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 µg/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.

Key Words: styrene ototoxicity; cochlear injury; hair cell death; apoptosis; caspase.


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