Nitric oxide synthase inhibitor suppresses the ototoxic side effect of cisplatin in guinea pigs.
Cisplatin is known to cause inner ear damage (ototoxicity). The role of inducible nitric oxide synthase (iNOS) in the cochlea of guinea pigs after injections of cisplatin or a combination of cisplatin and NOS inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) i.p. was examined electro-and immunohistochemically. The auditory brain stem responses (ABR) were measured prior to injection and 3 days after the injection. Three days after injection, the cochleas were examined immunohistochemically for iNOS. We found that iNOS was expressed in the cisplatin- and L-NAME/ cisplatin-treated cochlea. The threshold shift of ABR was significant in the cisplatin group, whereas it was decreased in the L-NAME/cisplatin group. iNOS catalyzed high NO levels lead to inner ear dysfunction. Our results indicate that iNOS mediates the ototoxicity of cisplatin.
Department of Oto-Rhino-Laryngology, Nippon Medical School, Tokyo, Japan. BXP02646@nifty.ne.jp
K I
KI
Watanabe
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A
Hess
W
W
Bloch
O
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Michel
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000201:enzymology; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006311:Hearing Disorders / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D007150:Immunohistochemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D002945:Cisplatin; D019331:NG-Nitroarginine Methyl Ester