Protective effects of alpha-tocopherol and tiopronin against cisplatin-induced ototoxicity.
OBJECTIVE
To investigate the possible protective effects of alpha-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 alpha-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage.


METHODS
Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+alpha-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+alpha-tocopherol acetate+tiopronin, (V) alpha-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. Alpha-tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with alpha-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 alpha-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of alpha-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed.


CONCLUSIONS
This study supports the hypothesis that alpha-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.
Fetoni
A R
AR
Institute of Otolaryngology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Sergi
B
B
Ferraresi
A
A
Paludetti
G
G
Troiani
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage*; D001309:Auditory Threshold; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects; D008625:Tiopronin / Q000008:administration & dosage*; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D000975:Antioxidants; D008625:Tiopronin; D024502:alpha-Tocopherol; D002945:Cisplatin