Nitric oxide synthase inhibitor reduces the apoptotic change in the cisplatin-treated cochlea of guinea pigs.
Cisplatin is known to cause inner ear damage. The role of nitric oxide (NO) in the cochlea of the guinea pigs after injections of cisplatin or a combination of cisplatin and NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)] i.p. was examined by means of immunohistochemistry. Three days after injection, the cochleas were examined immunohistochemically for single-stranded DNA (ssDNA). We found that ssDNA was expressed in the stria vascularis and spiral ganglion cells of the cisplatin-treated cochlea. In the L-NAME/cisplatin-treated cochlea, the number of cells that exhibited positive staining for ssDNA was markedly reduced. High NO levels lead to inner ear dysfunction under pathological conditions. Our results indicate that NO mediates the ototoxicity of cisplatin.
Watanabe
K
K
Department of Oto-Rhino-Laryngology, Nippon Medical School, Tokyo, Japan. bxp02646@nifty.ne.jp
Hess
A
A
Michel
O
O
Yagi
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D053938:DNA Fragmentation; D004277:DNA, Single-Stranded / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007150:Immunohistochemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D002945:Cisplatin; D019331:NG-Nitroarginine Methyl Ester