Anna Rita Fetoni1, Fabiola Paciello2, Rolando Rolesi3, Anna Pisani4, Arturo Moleti5, Renata Sisto6, Diana Troiani7, Gaetano Paludetti3, Claudio Grassi2. 1. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Department of Head and Neck Surgery, Università Cattolica Del Sacro Cuore, Roma, Italy. Electronic address: annarita.fetoni@unicatt.it. 2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Department of Neuroscience, Università Cattolica Del Sacro Cuore, Roma, Italy. 3. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Department of Head and Neck Surgery, Università Cattolica Del Sacro Cuore, Roma, Italy. 4. Department of Head and Neck Surgery, Università Cattolica Del Sacro Cuore, Roma, Italy. 5. Department of Physics, University of Roma Tor Vergata, Roma, Italy. 6. Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Italian Workers' Compensation Authority (INAIL), Monte Porzio Catone (RM), Italy. 7. Department of Neuroscience, Università Cattolica Del Sacro Cuore, Roma, Italy.
Abstract
BACKGROUND: Although styrene is an established ototoxic agent at occupational exposure levels, the mechanisms of styrene toxicity in the auditory system are still unclear. OBJECTIVES: The aim of this study was to identify the consequences of styrene chronic exposure in cochlear structures, looking for the mechanisms of ototoxicity of this organic compound and focusing on cell targets and oxidative stress/inflammatory processes. METHODS: Male adult Wistar rats were exposed to styrene (400 mg/kg by gavage for 5 days/week, 3 consecutive weeks). Hearing loss was evaluated by measuring auditory brainstem responses (ABR), morphological analysis were performed to evaluate hair cell and spiral ganglion neuron survival, as well as synaptic damage. Analysis of apoptotic (p53) and inflammatory (NF-κB, TNF-α, IL-1β and IL-10) mediators were performed by immunofluorescence analysis and western blot. RESULTS: Styrene ototoxic effects induced a hearing loss of about 35-40 dB. Immunofluorescence and western blotting analyses demonstrated that styrene administration induced redox imbalance and activated inflammatory processes, targeting sensory hair cell and neural dysfunction by a cross-talk between oxidative and inflammatory mediators. DISCUSSION: Major findings connect styrene ototoxicity to an interplay between redox imbalance and inflammation, leading to the intriguing assumption of a mixed sensory and neural styrene-induced ototoxicity. Thus, in a clinical perspective, data reported here have important implications for styrene risk assessment in humans.
BACKGROUND: Although styrene is an established ototoxic agent at occupational exposure levels, the mechanisms of styrenetoxicity in the auditory system are still unclear. OBJECTIVES: The aim of this study was to identify the consequences of styrene chronic exposure in cochlear structures, looking for the mechanisms of ototoxicity of this organic compound and focusing on cell targets and oxidative stress/inflammatory processes. METHODS: Male adult Wistar rats were exposed to styrene (400 mg/kg by gavage for 5 days/week, 3 consecutive weeks). Hearing loss was evaluated by measuring auditory brainstem responses (ABR), morphological analysis were performed to evaluate hair cell and spiral ganglion neuron survival, as well as synaptic damage. Analysis of apoptotic (p53) and inflammatory (NF-κB, TNF-α, IL-1β and IL-10) mediators were performed by immunofluorescence analysis and western blot. RESULTS:Styreneototoxic effects induced a hearing loss of about 35-40 dB. Immunofluorescence and western blotting analyses demonstrated that styrene administration induced redox imbalance and activated inflammatory processes, targeting sensory hair cell and neural dysfunction by a cross-talk between oxidative and inflammatory mediators. DISCUSSION: Major findings connect styreneototoxicity to an interplay between redox imbalance and inflammation, leading to the intriguing assumption of a mixed sensory and neural styrene-induced ototoxicity. Thus, in a clinical perspective, data reported here have important implications for styrene risk assessment in humans.
Authors: Renata Sisto; Arturo Moleti; Pasquale Capone; Filippo Sanjust; Luigi Cerini; Giovanna Tranfo; Giulia Massini; Sara Buscema; Paolo Massimo Buscema; Pieranna Chiarella Journal: Front Public Health Date: 2022-09-20