Gentamicin, acting as an
iron chelator, activates
membrane lipid peroxidation (MPL) and induces
free radical formation, as observed in vitro and in vivo.
Antioxidants, such as
alpha-tocopherol, are able to suppress MLP, thus attenuating tissue damage. The present study was designed to investigate the possible protective effects of
alpha-tocopherol on
gentamicin ototoxicity. The study was carried out on albino guinea pigs (250-350 g). The animals were divided into four groups: group A (n = 4), injected with
corn oil daily at a dose of 100 mg/kg
body weight intramuscularly (IM); group B (n = 10), treated with
corn oil at a dose of 100 mg/kg
body weight and
gentamicin base at a dose of 100 mg/kg
body weight (IM); group C (n = 10). treated with
gentamicin alone at a dose of 100 mg/kg
body weight (IM); and group D (n = 10), treated with
gentamicin at the same dose plus
alpha-tocopherol acetate at dose of 100 mg/kg
body weight (IM). Electrocochleographic recordings were made from an implanted round-window
electrode. All animals were treated for 14 days. The compound action potentials (CAPs) were measured at 2-16 kHz at days 0, 10, 14 and 18
after treatment. Changes in cochlear function were characterized as CAP threshold shifts. Morphological changes were analysed by scanning electron microscopy.
Gentamicin induced progressive
high-frequency hearing loss of 50-60 dB SPL.
alpha-Tocopherol co-
therapy slowed the progression of
hearing loss. The significant loss of outer hair cells (OHCs) in the cochlear basal turn in
gentamicin-treated animals was not observed in the cochleas of animals protected with
alpha-tocopherol. This study supports the hypothesis that
alpha-tocopherol interferes with
gentamicin-induced
free radical formation, and suggests that this
drug may be useful in protecting OHC function from
aminoglycoside ototoxicity, thus reducing
hearing loss.