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Aminoguanidine reduces cisplatin ototoxicity
Thomas C Kelly1, Craig A Whitworth, Kazim Husain
1Southern Illinois University School of Medicine, Department of Surgery, P.O. Box 19638, Springfield, IL 62794-9653, USA.
Hearing Research
|December 4, 2003
Summary
Aminoguanidine (AG) partially protected against cisplatin-induced hearing loss in rats by scavenging free radicals. This suggests reactive oxygen species, not nitric oxide, are the primary mediators of cisplatin ototoxicity.
Area of Science:
- Ototoxicity research
- Neuroscience
- Pharmacology
Background:
- Cisplatin chemotherapy can cause high-frequency hearing loss.
- Reactive oxygen species are implicated in cisplatin ototoxicity.
- The role of reactive nitrogen species in cisplatin ototoxicity remains unclear.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in cisplatin-induced ototoxicity.
- To determine if aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) inhibitor, can mitigate cisplatin ototoxicity.
Main Methods:
- Rats received cisplatin, AG, or both.
- Auditory brainstem evoked responses (ABR) measured hearing thresholds.
- Cochlear tissue analyzed for NO and malondialdehyde levels.
Main Results:
- Cisplatin induced significant ABR threshold shifts.
- AG alone did not affect hearing thresholds.
- AG co-administration reduced threshold shifts for clicks and 16 kHz stimuli.
- Malondialdehyde levels decreased in the AG/cisplatin group, but NO levels did not.
Conclusions:
- AG may reduce cisplatin ototoxicity by scavenging hydroxyl radicals.
- The inducible nitric oxide synthase (iNOS) pathway's role in cisplatin ototoxicity was not supported by these findings.