Korean J Otolaryngol-Head Neck Surg.  2002 Aug;45(8):741-746.

The Ototoxicity of Cisplatin is Mediated by NO: A Study using L-NAME and MK-801 in Guinea pigs

• Rhee CK
• Oh YH
• Jeon SJ
• Chung SY
• Oh CH

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.

Keyword

Cisplatin; NG-Nitroarginine methyl ester; Dizocilpine maleate; Nitric oxide

MeSH Terms

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
Cisplatin
Dizocilpine Maleate
N-Methylaspartate
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase