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Protective effects of α-tocopherol and tiopronin against cisplatin-induced ototoxicity
Objective To investigate the possible protective effects of α-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species...
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Published in: | Acta oto-laryngologica 2004-05, Vol.124 (4), p.421-426 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Objective
To investigate the possible protective effects of α-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as α-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage.
Material and Methods
Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+α-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+α-tocopherol acetate+tiopronin, (V) α-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels.
Results
Cisplatin induced progressive high-frequency hearing loss of 40-50 dB SPL. α-Tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with α-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both α-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of α-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed.
Conclusion
This study supports the hypothesis that α-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss. |
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ISSN: | 0001-6489 1651-2251 |
DOI: | 10.1080/00016480410016559 |