Effect over time of allopurinol on noise-induced hearing loss in guinea pigs: Efecto en el tiempo del alopurinol sobre la hipoacusia inducida por ruido en cobayos

This study investigates the correlation between the formation of reactive oxygen species (ROS) and auditory damage in noise-induced hearing loss. The noise exposure (4-kHz octave band, 115 dB SPL, 5 h) created permanent threshold shifts at frequencies from 2 to 20 kHz. The lipid peroxidation product, 8-isoprostane, was determined biochemically and histochemically as an indicator of ROS. Noise exposure increased 8-isoprostane levels in the cochlea in a time-dependent manner. After 5 h of exposure, 8-isoprostane levels were more than 30-fold greater than baseline, and decreased rapidly after the termination of noise. The immunoreactivity to 8-isoprostane was increased in the stria vascularis, spiral ganglion cells and the organ of Corti. In the organ of Corti, immunostaining was restricted to the second turn in a region 10-12 mm from the apex. This region sustained most of the permanent hair cell damage as revealed in surface preparations. Outer hair cells were more heavily immunostained than inner hair cells while Hensen's cells showed still less immunostain. These data are consistent with the view that ROS are involved in noise-induced damage. However, the relationship between ROS formation and tissue damage appears complex. In the organ of Corti, the pattern of noise-induced lipid peroxidation correlates well with subsequent morphological damage. The stria vascularis, however, does not sustain permanent damage despite intense lipid peroxidation. Differences in endogenous antioxidant levels and commitment to different apoptotic or survival pathways may underlie such differential responses.

Exposure to low level noise prior to a high level exposure reduces noise-induced hearing loss in mammals. This phenomenon is known as sound conditioning or 'toughening'. Reactive oxygen intermediates have been implicated in noise-induced cochlear damage. To evaluate if in situ antioxidant processes may play a role in the toughening phenomenon initiated by low level noise exposure we analyzed glutathione reductase, gamma-glutamyl cysteine synthetase, and catalase in stria vascularis and organ of Corti fractions from cochleae of chinchillas exposed to a sound conditioning paradigm. Chinchillas were either (A) kept in quiet cages (control), (B) exposed to conditioning noise of a 0.5 kHz octave band (90 dB for 6 h/day for 10 days), (C) exposed to high level noise (105 dB for 4 h) or (D) exposed to conditioning noise (B) followed by exposure to the higher level noise (C). Each of the noise exposure conditions (B, C, D) induced changes in the levels of these three antioxidant enzymes. The enzyme-specific activity data for the four subject groups support the following two hypotheses. (1) Changes in glutathione reductase, gamma-glutamyl cysteine synthetase, and catalase play a role in attenuating hearing loss associated with sound conditioning followed by high level noise. (2) Hair cells in the organ of Corti are protected from noise-induced damage by increasing stria vascularis levels of catalase, a hydrogen peroxide scavenging enzyme, and of enzymes involved in maintaining glutathione in the reduced state. The model formulated by these hypotheses suggests that agents that protect or augment the glutathione system in the cochlea may be protective against noise-induced hearing loss.

Allopurinol is a scavenger of the highly reactive hydroxyl radical (k2 approx. 10(9) M-1 X s-1). One product of attack of hydroxyl radical upon allopurinol is oxypurinol, which is a major metabolite of allopurinol. Oxypurinol is a better hydroxyl radical scavenger than is allopurinol (k2 approx. 4 X 10(9) M-1 X s-1) and it also reacts with the myeloperoxidase-derived oxidant hypochlorous acid. Hence the protective actions of allopurinol against reperfusion damage after hypoxia need not be entirely due to xanthine oxidase inhibition.