Glutathione-dependent antioxidant systems in the mammalian inner ear: effects of aging, ototoxic drugs and noise

Abstract

Glutathione and glutathione-related enzymes protect against oxidative (free radical) cell injury. This study presents basic information on this antioxidant system in inner ear tissues and preliminary results of the influence of age, ototoxic drugs and noise. These conditions affect inner ear function, possibly through free radicals, and are therefore expected to affect cellular defense mechanisms. In 24-month old Fischer 344 rats, a standard model for aging, glutathione levels were significantly decreased in the auditory nerve by 86% as compared to 3-month old rats but remained unchanged in other cochlear tissues. In guinea pig, the common model for drug- and noise-induced trauma, glutathione levels in the cochlear sensory epithelium were about 8-fold higher (223 ±35 nmol glutathione/mg protein) than in the rat. Cochlear glutathione S-transferase and glutathione reductase activities were similar between the two species, whereas selenium-independent glutathione peroxidase was strikingly lower in guinea pig than in rat (9 ± 3 nmol vs. 161 ± 84 nmol glutathione converted/mg protein/min). Cisplatin treatment of guinea pigs (56 dB threshold shift at 18 kHz) significantly lowered cochlear glutathione levels by 65% and glutathione S-transferase activity by 44%. Gentamicin treatment (80 dB threshold shift at 18 kHz) and noise exposure (43 dB threshold shift at 18 kHz) did not affect glutathione at the tissue level. These results demonstrate species differences in cochlear glutathione and glutathione-related enzymes. The antioxidant system is sensitive towards environmental influences as seen for age and cisplatin. For gentamicin and noise trauma, whole tissue glutathione and enzyme levels do not correlate with functional damage. This indicates that glutathione homeostasis is largely maintained in the cochlea and that biochemical changes, if they occur under these conditions, may be limited to specific cells.