ABSTRACT
BACKGROUND AND OBJECTIVES: In general, aminoglycosides are known to cause ototoxicity through the glutamate induced nitric oxide production. The N-methyl-D-aspartate (NMDA) related glutamate receptors have a pivotal role in aminoglycoside induced ototoxicity. Memantine is known as a safe NMDA antagonist and is also used in some neurologic insults, such as the Alzheimer disease. In this study, we observed the effect of memantine on gentamicin induced vestibulotoxicity in an animal model. MATERIALS AND METHOD: Vestibulotoxicity was induced with intratympanic administration of gentamicin and memantine was injected intraperitoneally to a study group. Histomorphological studies for vestibule were performed via light and electron microscopy. Immunohistochemical studies were performed for iNOS, nitrotyrosine and apoptosis via TUNEL staining. RESULTS: The numbers of hair cells were decreased significantly in the gentamicin group than in the gentamicin-memantine group. Increased immunoreactivities for iNOS and nitrotyrosine were observed in the gentamicin group than in the memantine-pretreated gentamicin group. TUNEL positive cells were more frequently observed in the gentamicin group than in the memantinepretreated gentamicin group. CONCLUSION: This result shows that memantine has a protection effect on gentamicin-induced vestibulotoxicity in an animal model.
Subject(s)
Animals , Alzheimer Disease , Aminoglycosides , Apoptosis , Gentamicins , Glutamic Acid , Guinea , Guinea Pigs , Hair , In Situ Nick-End Labeling , Light , Memantine , Microscopy, Electron , Models, Animal , N-Methylaspartate , Nitric Oxide , Receptors, Glutamate , TyrosineABSTRACT
BACKGROUND AND OBJECTIVES: p27(Kip1), a novel cyclin-dependent kinase inhibitor, plays a crucial role in regulation of cell proliferation during development of inner ear. In addition, p27(Kip1) is known to regulate cell death in avian auditory epithelia. However, only a little is known about its role in aminoglycoside-induced mammalian vestibular degeneration. The aim of this study was to examine roles of p27(Kip1) in gentamicin-induced vestibulotoxicity. MATERIALS AND METHOD: C57BL/6J mice were used as experimental animals. Ampullar cristae damaged by local application of gentamicin were provided for histological analyses and western blotting. TUNEL assay was used to detect apoptosis. Immunohistochemistry and western blotting for p27(Kip1) were performed to investigate its expression. RESULTS: TUNEL-positive cells were detected in the hair cells of gentamicin-treated mice. Expression of p27(Kip1) was found in the supporting cells, but not in the hair cells. Gentamicin treatment caused degeneration of vestibular hair cells, and a decrease of numbers of p27(Kip1)-positive cells. The western blotting showed that expression of p27(Kip1) was markedly decreased on day 3. CONCLUSION: The present findings indicate that p27(Kip1) may play roles in repair of hair cells by regenerative proliferation or transdifferentiation of supporting cells, but not in cell death of hair cells.
Subject(s)
Animals , Mice , Apoptosis , Blotting, Western , Cell Death , Cell Proliferation , Ear, Inner , Gentamicins , Hair , Hair Cells, Vestibular , Immunohistochemistry , In Situ Nick-End Labeling , PhosphotransferasesABSTRACT
The histopathological alterations in the vestibule due to aminoglycosides are well defined. Although there are reports comparing the vestibulotoxic effects of the many aminoglycosides, this is the first study to compare the effects of the most commonly used aminoglycosides i.e., streptomycin, gentamicin, amikacin and netilmicin administered both transtympanically and systemically. The transtympanic and systemic administration of each aminoglycoside caused similar histopathological alterations in the vestibule. The most severe degeneration in the cristae ampullaris, utriculus and sacculus was observed after streptomycine administration. The severity of the vestibular damage in terms of magnitude was in the order of streptomycine, gentamicin, amikacin, and netilmicin.