BACKGROUND: Cisplatin is reported to damage the stria vascularis of the cochlea. Free radicals, especially large amounts of nitric oxide catalyzed by inducible nitric oxide synthase, are considered to have an important role in this toxicity. The induction of inducible nitric oxide synthase is regulated by nuclear-factor kappa B (NF-kappa B). We examined the damage of the stria vascularis by immunohistochemical techniques. MATERIALS AND METHODS: Cisplatin (15 mg/kg b.w.) was injected intraperitoneally into the mice. Three days after the injection, the cochleas were immunohistochemically-stained using specific antibodies for nuclear-factor kappa B (NF-kappa B), inducible nitric oxide synthase (iNOS) or single-stranded DNA. RESULTS: NF-kappa B was expressed in the cisplatin-treated cochlea, especially in the stria vascularis and the spiral ligament. iNOS was also expressed in the stria vascularis and the spiral ligament. Fragments of DNA were observed only in the stria vascularis. CONCLUSION: The large amounts of NO catalyzed by iNOS led to inner ear dysfunction. Our results indicate that apoptosis is triggered by iNOS and that it mediates the ototoxicity induced by cisplatin.
BACKGROUND:Cisplatin is reported to damage the stria vascularis of the cochlea. Free radicals, especially large amounts of nitric oxide catalyzed by inducible nitric oxide synthase, are considered to have an important role in this toxicity. The induction of inducible nitric oxide synthase is regulated by nuclear-factor kappa B (NF-kappa B). We examined the damage of the stria vascularis by immunohistochemical techniques. MATERIALS AND METHODS:Cisplatin (15 mg/kg b.w.) was injected intraperitoneally into the mice. Three days after the injection, the cochleas were immunohistochemically-stained using specific antibodies for nuclear-factor kappa B (NF-kappa B), inducible nitric oxide synthase (iNOS) or single-stranded DNA. RESULTS:NF-kappa B was expressed in the cisplatin-treated cochlea, especially in the stria vascularis and the spiral ligament. iNOS was also expressed in the stria vascularis and the spiral ligament. Fragments of DNA were observed only in the stria vascularis. CONCLUSION: The large amounts of NO catalyzed by iNOS led to inner ear dysfunction. Our results indicate that apoptosis is triggered by iNOS and that it mediates the ototoxicity induced by cisplatin.
Authors: Debashree Mukherjea; Sarvesh Jajoo; Craig Whitworth; Jennifer R Bunch; Jeremy G Turner; Leonard P Rybak; Vickram Ramkumar Journal: J Neurosci Date: 2008-12-03 Impact factor: 6.167