Protective effects of alpha-tocopherol against gentamicin-induced Oto-vestibulo toxicity: an experimental study.
OBJECTIVE
Free radicals are involved in gentamicin ototoxicity and vestibular dysfunction and it has been demonstrated that free radical scavengers, such as alpha-tocopherol, are able to inactive free radicals, attenuating tissue damage This study was designed to investigate the possible protective effects of alpha-tocopherol against gentamicin-induced oto-vestibulo toxicity.


METHODS
Adult albino guinea pigs were divided into four groups and were treated for 2 weeks as follows: Group A, controls; Group B, gentamicin plus corn oil; Group C, gentamicin only; and Group D, gentamicin plus alpha-tocopherol. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VORs), respectively. Electrocochleographic recordings were performed using an implanted round window electrode. The compound action potentials (CAPs) at 2, 4, 8 and 16 kHz were measured every 5 days Morphological changes were analysed by means of scanning electron microscopy.


RESULTS
Gentamicin induced a consistent reduction in VOR responses and a progressive high-frequency hearing loss of 50-60 dB sound pressure level. Alpha-Tocopherol co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shifts The impairment of vestibular function was reduced, as evidenced by an increased VOR gain. The massive loss of outer hair cells in the cochlear basal turn and of cristae ampullaris stereocilia in gentamicin-treated animals was not observed in the cochlea of animals protected with alpha-tocopherol.


CONCLUSIONS
This study supports the hypothesis that alpha-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in preventing aminoglycoside oto-vestibulo toxicity.
Fetoni
Anna Rita
AR
Institute of Otolaryngology, Catholic University of Rome, Rome, Italy. afetoni@libero.it
Sergi
Bruno
B
Scarano
Emanuele
E
Paludetti
Gaetano
G
Ferraresi
Aldo
A
Troiani
Diana
D
D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D004195:Disease Models, Animal; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D007758:Ear, Inner / Q000187:drug effects / Q000648:ultrastructure; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005839:Gentamicins / Q000494:pharmacology / Q000633:toxicity*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008855:Microscopy, Electron, Scanning; D011336:Probability; D012016:Reference Values; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects / Q000502:physiology; D014722:Vestibule, Labyrinth / Q000187:drug effects* / Q000648:ultrastructure; D024502:alpha-Tocopherol / Q000494:pharmacology*
D005839:Gentamicins; D024502:alpha-Tocopherol