The Ototoxicity of Cisplatin is Mediated by NO: A Study using L-NAME and MK-801 in Guinea pigs.
- Author:
Chung Ku RHEE
1
;
Yang Hee OH
;
Sang Jun JEON
;
Sang Yong CHUNG
;
Chung Hun OH
Author Information
1. Departments of Otorhinolaryngology-Head & Neck Surgery, Medical Laser Research Center, Dankook University College of Medicine, Cheonan, Korea. JSJ2000@hanmail.net
- Publication Type:Original Article
- Keywords:
Cisplatin;
NG-Nitroarginine methyl ester;
Dizocilpine maleate;
Nitric oxide
- MeSH:
Animals;
Cisplatin*;
Cochlea;
Dizocilpine Maleate*;
Evoked Potentials, Auditory, Brain Stem;
Guinea Pigs*;
Guinea*;
Hair;
Hearing;
Hearing Loss;
Microscopy, Electron, Scanning;
N-Methylaspartate;
NG-Nitroarginine Methyl Ester*;
Nitric Oxide;
Nitric Oxide Synthase;
Stereocilia
- From:Korean Journal of Otolaryngology - Head and Neck Surgery
2002;45(8):741-746
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND AND OBJECTIVES: Nitric oxide has been suggested to play an important role in the pathogenesis of cisplatin ototoxicity. L-NAME (NG-Nitroarginine Methyl Ester) is an inhibitor of nitric oxide synthase. MK-801 (Dizocilpine Maleate) is a NMDA receptor antagonist. To evaluate a role of nitric oxide in cisplatin ototoxicity, we investigated whether L-NAME and MK-801 can block the cisplatin ototoxicity in guinea pigs. MATERIALS AND METHOD: In the Group 1, normal saline was injected intraperitoneally as a control group. Group 2, 3, 4, and 5 were injected intraperitoneally as described in the following: Group 2, cisplatin only; Group 3, L-NAME+isplatin; Group 4, MK-801+cisplatin; Group 5, L-NAME+K-801+cisplatin. Using an auditory brainstem response, hearing threshold was tested before cisplatin administration and 5 days after cisplatin injection in each group. The morphological changes of the cochlea were observed by scanning electron microscopy. RESULTS: In the Group 2, a significant hearing loss was observed comparing to Group 1. In contrast , Group 3, 4, and 5 did not demonstrate any significant hearing loss compared to Group 1. In the scanning electron microscopy, the Group 2 showed distorsion and loss of stereocilia of the hair cells. However, the Group 1, 3, 4, and 5 demonstrated well preserved cochlear hair cell morphology. CONCLUSION: Hearing loss induced by ototoxicity of cisplatin was prevented by L-NAME and MK-801. This study suggests that NO may mediate cisplatin ototoxicity.
