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실험적으로 유도한 Gentamicin 전정독성 기니픽 모델에서 Memantine의 효과

The Effect of Memantine on Experimentally Gentamicin Induced Vestibulotoxicity in Guinea Pigs

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주제분류이비인후과학

초록

Background and ObjectivesZZIn 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 MethodZZVestibulotoxicity 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. ResultsZZThe 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. ConclusionZZThis result shows that memantine has a protection effect on gentamicin-induced vestibulotoxicity in an animal model. Korean J Otorhinolaryngol-Head Neck Surg 2010;53:77-83

Abstract

Background and ObjectivesZZIn 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 MethodZZVestibulotoxicity 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. ResultsZZThe 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. ConclusionZZThis result shows that memantine has a protection effect on gentamicin-induced vestibulotoxicity in an animal model. Korean J Otorhinolaryngol-Head Neck Surg 2010;53:77-83

참고문헌 (19)

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  7. Reisberg B, "Memantine in moderate-to-severe Alzheimer’s disease", N Engl J Med, 348(14), pp.1333~1341 (2003)
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  9. Puyal J, "Distribution of alphaamino- 3-hydroxy-5-methyl-4 isoazolepropionic acid and N-methyl- D-aspartate receptor subunits in the vestibular and spiral ganglia of the mouse during early development", Brain Res Dev Brain Res, 139(1), pp.51~57 (2002)
  10. Takumida M, "Glutamate-induced production of nitric oxide in guinea pig vestibular sensory cells", Acta Otolaryngol, 120(4), pp.466~472 (2000)
  11. Takumida M, "Nitric oxide in guinea pig vestibular sensory cells following gentamicin exposure in vitro", Acta Otolaryngol, 121(3), pp.346~350 (2001)
  12. Snyder SH, "Biological roles of nitric oxide", Sci Am, 266(5), pp.68~71 (1992)
  13. Hong SH, "Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents in the guinea pig", Hear Res, 211(2), pp.46~53 (2006)
  14. Kuhn DM, "Nitrotyrosine as a marker for peroxynitrite-induced neurotoxicity: the beginning or the end of the end of dopamine neurons?", J Neurochem, 89(3), pp.529~536 (2004)
  15. Duan M, "Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity", Proc Natl Acad Sci USA, 97(13), pp.7597~7602 (2000)
  16. Hakuba N, "AMPA", kainate-type glutamate receptor antagonist reduces progressive inner hair cell loss after transient cochlear ischemia, 2003, pp.979(2), 194~202
  17. Chen Z, "Acute treatment of noise trauma with local caroverine application in the guinea pig", Acta Otolaryngol, 123(8), pp.905~909 (2003)
  18. Duan M, "Lowdose, long-term caroverine administration attenuates impulse noiseinduced hearing loss in the rat", Acta Otolaryngol, 126(11), pp.1140~1147 (2006)
  19. Chen HS, "Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity", J Neurosci, 12(11), pp.4427~4436 (1992)

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