title: Styrene enhances the noise induced oxidative stress in the cochlea and affects differently mechanosensory and supporting cells.
abstract: Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens. The mechanism of damage was studied by analyzing superoxide anion and lipid peroxidation expression and by computational analyses of immunofluorescence data to evaluate and compare the oxidative stress pattern in outer hair cells versus the supporting epithelial cells of the organ of Corti. The oxidative stress hypothesis was further analyzed by evaluating the protective effect of a Coenzyme Q10analogue, the water soluble Qter, molecule known to have protective antioxidant properties against noise induced hearing loss and by the analysis of the expression of the endogenous defense enzymes. This study provides evidence of a reciprocal noise-styrene synergism based on a redox imbalance mechanism affecting, although with a different intensity of damage, the outer hair cell (OHC) sensory epithelium. Moreover, these two damaging agents address preferentially different cochlear targets: noise mainly the sensory epithelium, styrene the supporting epithelial cells. Namely, the increase pattern of lipid peroxidation in the organ of Corti matched the cell damage distribution, involving predominantly OHC layer in noise exposed cochleae and both OHC and Deiters' cell layers in the styrene or combined exposed cochleae. The antioxidant treatment reduced the lipid peroxidation increase, potentiated the endogenous antioxidant defense system at OHC level in both exposures but it failed to ameliorate the oxidative imbalance and cell death of Deiters' cells in the styrene and combined exposures. Current antioxidant therapeutic approaches to preventing sensory loss focus on hair cells alone. It remains to be seen whether targeting supporting cells, in addition to hair cells, might be an effective approach to protecting exposed subjects.
authors: Institute of Otolaryngology, Università Cattolica School of Medicine, Rome, Italy; Institute of Cell Biology and Neurobiology, CNR, Monterotondo, Italy. Electronic address: AnnaRita.Fetoni@unicatt.it.
authors: A R
authors: AR
authors: Fetoni
authors: Institute of Otolaryngology, Università Cattolica School of Medicine, Rome, Italy.
authors: R
authors: R
authors: Rolesi
authors: Institute of Otolaryngology, Università Cattolica School of Medicine, Rome, Italy; Institute of Cell Biology and Neurobiology, CNR, Monterotondo, Italy.
authors: F
authors: F
authors: Paciello
authors: Institute of Human Physiology, Università Cattolica School of Medicine, Rome, Italy.
authors: S L M
authors: SLM
authors: Eramo
authors: Institute of Human Physiology, Università Cattolica School of Medicine, Rome, Italy.
authors: C
authors: C
authors: Grassi
authors: Institute of Human Physiology, Università Cattolica School of Medicine, Rome, Italy.
authors: D
authors: D
authors: Troiani
authors: Institute of Otolaryngology, Università Cattolica School of Medicine, Rome, Italy.
authors: G
authors: G
authors: Paludetti
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D007760:Labyrinth Supporting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009622:Noise / Q000009:adverse effects*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D020058:Styrene / Q000633:toxicity*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014451:Ubiquinone; D020058:Styrene; C024989:coenzyme Q10
keywords: Antioxidants; Inner ear; Organic solvents; Redox imbalance