Gentamicin Increases Nitric Oxide Production and Induces Hearing Loss in Guinea Pigs

Abstract

Gentamicin application is an important therapeutic option for Ménière's disease. However, even if given at intervals, a destruction of the cochlea was often observed in various animal models together with an increased content of nitric oxide (NO) and reactive oxygen species. The present study was undertaken to identify the correlation between hearing threshold alteration and the NO production in the lateral wall and organ of Corti of the guinea pig in response to gentamicin application. Prospective animal study in guinea pigs. A single dose of gentamicin (10 mg/kg body weight) was injected intratympanally into male guinea pigs and the auditory brainstem responses were recorded before treatment and 1, 2, and 7 days after application. The organ of Corti and the lateral wall were removed from the bulla, incubated separately for 6 hours in cell culture medium and the amount of NO production was determined by chemiluminescence. Gentamicin application resulted in a hearing threshold shift beginning on the second day after gentamicin application. This hearing impairment correlates simultaneously with an increased NO2(-) content--the stable oxidation product of NO--in the lateral wall. In the organ of Corti, a slight increase in NO2(-) production was seen as early as on day 1 after gentamicin injection. The correlation between hearing threshold shift and NO production in the cochlea leads to the assumption that increased NO contributes to gentamicin-induced hearing impairment.