2-amino-4-hydroxy-6-formylpteridine and Hearing-Loss--Noise-Induced

Potentiation of noise-induced hearing loss (NIHL) by specific chemical contaminants and therapeutic drugs represents a distinct public health risk. Prediction of chemicals that yield such potentiation has not been successful because such agents differ markedly in structure. One mechanism for this potentiation that has garnered support is oxidative injury to the cochlea. Thus far, limited data have been published in support of this hypothesis. The current experiment was designed to further test this model using two antioxidant compounds, lipoic acid (LA) and 6-formylpterin (6-FP), and determine whether they would block potentiation of NIHL resulting from simultaneous exposures to carbon monoxide (CO) and noise in rats. Neither CO nor noise exposure at the intensity and duration selected produce persistent auditory impairment by themselves. Different groups of rats were exposed to noise alone centered at 8.0 kHz (105 dB) for 2 hours or to combined CO + noise treatment consisting of CO exposure for 1.5 hours and then exposure to CO + noise for 2 hours. Additional groups received either LA (100 mg/kg) or 6-FP (14 mg/kg) 30 minutes prior to the onset of CO + noise. Cochlear function was monitored using distortion product otoacoustic emissions, and auditory thresholds were assessed using compound action potentials recorded from the round window. Histopathological evaluation of the organ of Corti provided counts of missing hair cells in each treatment group. The CO + noise-exposure group replicated previous studies in demonstrating permanent impairment of cochlear function and associated outer hair cell loss that greatly exceeded the minimal losses observed in the group treated with noise alone. Both LA and 6-FP given 30 minutes prior to the onset of CO + noise exposure reduced cochlear impairment and loss of hair cells.

Topics: Animals; Carbon Monoxide; Disease Models, Animal; Hair Cells, Auditory; Hearing Loss, Noise-Induced; Male; Pterins; Rats; Thioctic Acid