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Original Article

α-Tocopherol protective effects on gentamicin ototoxicity: an experimental study

Efectos protectores del α-Tocoferol en la toxicidad por gentamicina: un estudio experimental

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Pages 166-171 | Received 10 Jul 2002, Accepted 13 Mar 2003, Published online: 07 Jul 2009
 

Abstract

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 α-tocopherol, are able to suppress MLP, thus attenuating tissue damage. The present study was designed to investigate the possible protective effects of α-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 α-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. α-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 α-tocopherol. This study supports the hypothesis that α-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.

Sumario

La gentamicina como quelante de hierro, activa la peroxidación de la membrana lipídica (MPL) e induce la formación de los radicales libres, como se ha observado in vitro e in vivo. Los antioxidantes como el α tocoferol son capaces de suprimir la MPL, y por lo tanto atenuar el daño tisular. Este estudio fue diseñado para investigar los posibles efectos protectores del α tocoferol en la ototoxicidad de la gentamicina. El estudio se llevó a cabo en cobayos albinos (250–350 g). Los animales fueron divididos en cuatro grupos: grupo A (n = 4), inyectados intramuscularmente (IM) a diario con aceite de maiz a 100 mg/kg de peso; grupo B (n = 10), tratados con aceite de maiz a 100 mg/kg de peso y gentamicina base a 100 ng/kg (IM); grupo C (n = 10), tratados con gentamicina sola a 100 mg/kg (IM); y grupo D (n = 10), tratados con gentamicina a la misma dosis, más acetato de α-tocoferol a 100 mg/kg (IM). Se tomaron registros electrococleográficos a partir de un electrodo colocado en la ventana redonda. Todos los animales fueron tratados durante 14 días. Se midieron los potenciales de acción compuesta (CAPs) a 2–16 kHz los días 0, 10, 14 y 18 después del tratamiento. Los cambios en la función coclear se describieron como cambios del umbral de los CAP. Se analizaron los cambios morfológicos por medio de un barrido de microscopía electrónica. La gentamicina induce una hipoacusia progresiva para frecuencias agudas de 50–60 dB SPL. La terapia combinada con α-tocoferol disminuyó la progresión de la hipoacusia. La pérdida significativa de células ciliadas externas (OHCs) en la vuelta basal de las cócleas de los animales tratados con gentamicina no se observó en las cócleas de los animales protegidos con α-tocoferol. Este estudio apoya la hipótesis de que el α-tocoferol interfiere en la formación de radicales libres inducida por la gentamicina y sugiere que esta sustancia puede ser útil para la protección de la función de las OHC de la ototoxicidad por aminoglucósidos, con lo que se reduce la hipoacusia.

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