Abstract
Despite their ototoxic potential, aminoglycosides are commonly used for the treatment of serious gram-negative bacterial infections such as cystic fibrosis and life-threatening conditions such as sepsis. Currently, there is no effective treatment for the adverse side effects that can develop, such as aminoglycoside-induced ototoxicity, resulting in permanent hearing loss and balance disorders. Moreover, in-vitro studies that have evaluated and compared aminoglycoside-induced toxicity in both the cochlea and vestibular system are limited. Therefore, to delineate aminoglycosides’ toxic profile, the cochlear and vestibular toxicity of the aminoglycosides, gentamicin and amikacin, were evaluated and compared simultaneously using an in-vitro rat cochlear and utricular explant culture model. For this purpose, the inner ear explants were treated with different concentrations of aminoglycosides (0.3 - 2.4 mM) and the hair cell loss was evaluated using a fluorescent microscope. As inflammation is one of the relatively unexplored mechanisms behind aminoglycoside-induced toxicity, the otoprotective potential of an anti-inflammatory agent, Total Glucoside of Paeony (TGP) (100 µg/ml), was assessed following the aminoglycoside treatment. Gentamicin was found to be more toxic to both the cochlea and vestibular system than amikacin, and relatively greater gentamicin and amikacin-induced damage was observed in the cochlea compared to the vestibular system. Interestingly, the TGP treatment was found to ameliorate aminoglycoside-induced vestibular but not cochlear toxicity so, the differences between the underlying mechanisms of aminoglycoside-induced inflammation in the cochlear and vestibular systems are deemed worthy of further study.