Protective effects of α-tocopherol and tiopronin against cisplatin-induced ototoxicity
- 1 May 2004
- journal article
- research article
- Published by Taylor & Francis Ltd in Acta Oto-Laryngologica
- Vol. 124 (4), 421-426
- https://doi.org/10.1080/00016480410016559
Abstract
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.Keywords
This publication has 21 references indexed in Scilit:
- Treatment of Metastatic Head and Neck Cancer: Chemotherapy and Novel AgentsCancer Treatment and Research, 2002
- Part I: Chemotherapy for epithelial ovarian cancer–treatment at first diagnosisThe Lancet Oncology, 2002
- Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studiesInternational Journal of Radiation Oncology*Biology*Physics, 2001
- Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochleaHearing Research, 2000
- Protection of Both Auditory Hair Cells and Auditory Neurons from Cisplatin Induced DamageActa Oto-Laryngologica, 1997
- Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explantsHearing Research, 1996
- Differential Damage to Auditory Neurons and Hair Cells by Ototoxins and Neuroprotection by Specific Neurotrophins in Rat Cochlear Organotypic CulturesEuropean Journal of Neuroscience, 1996
- Role of Glutathione for Cisplatin Nephrotoxicity in Young and Adult RatsRenal Failure, 1993
- Changes in the stria vascularis of the guinea pig due to cis-platinumEuropean Archives of Oto-Rhino-Laryngology, 1984
- Cis‐Diamminedichloroplatinum (II) Ototoxicity in the Guinea PigOtolaryngology -- Head and Neck Surgery, 1981