RESUMEN
OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate possible preventive effects of anti-intercellular adhesion molecule-1 antibody (anti-ICAM-1 Ab) on noise-induced cochlear damage as assessed by changes in auditory thresholds and cochlear blood flow. STUDY DESIGN: A controlled animal study. Pretreated rats with anti-ICAM-1 Ab or saline control, followed with exposure to 72 continuous hours of broad band noise (107 dB SPL), and 24 hours after noise exposure treated again with anti-ICAM-1 Ab or saline. METHODS: Eighteen healthy male Fischer rats (200-250 g) were used. Sixteen were randomly selected to study noise-induced temporary threshold shifts. The remaining two rats were used to study cochlear blood flow (CBF), using laser Doppler flowmetry and blood pressure measurements. RESULTS: Rats treated with anti-ICAM-1 Ab (1.875 mg/kg, intravenously) showed attenuated temporary threshold shifts (TTS) compared to controls. Both groups showed a partial threshold recovery 72 hours following noise exposure, normal for this noise exposure paradigm. Comparisons of baseline and post-treatment measurements of CBF and mean arterial blood pressure revealed no significant changes. Anti-ICAM-1 Ab animals displayed significantly lower mean auditory threshold shifts at all five test frequencies (P < .05) when compared to control. CONCLUSIONS: Blocking the cascade of reactive oxygen species (ROS) generation by using anti-ICAM-Ab protects against noise-induced hearing loss.
Asunto(s)
Anexina A2/uso terapéutico , Cóclea/irrigación sanguínea , Pérdida Auditiva Provocada por Ruido/tratamiento farmacológico , Molécula 1 de Adhesión Intercelular/inmunología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Proteínas S100/uso terapéutico , Animales , Umbral Auditivo/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Ruido , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with the aging process and is the leading cause of adult auditory deficiency in the USA. Presbyacusis is described as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. Approximately 23% of the population between 65 and 75 years of age, and 40% of the population older than 75 years of age are affected by this condition. It was estimated in 1980 that 11% of the population was 76 years or older and this number is expected to almost double by the year 2030. When one considers that the population over 65 years of age is experiencing the most accelerated development of hearing loss, the potential socioeconomic ramifications are staggering. Curiously, the frequency of presbyacusis varies across different societies. This discrepancy has been attributed to many factors including genetics, diet, socioeconomic factors, and environmental variables. The purpose of this article is to review the various molecular mechanisms underlying presbyacusis and to offer insights into potential methods of mitigating the effects of aging on hearing impairment.
Asunto(s)
Daño del ADN , ADN Mitocondrial , Presbiacusia/genética , Presbiacusia/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Eliminación de Gen , Humanos , MutaciónRESUMEN
OBJECTIVE: The purpose of the study is to test the ability of resveratrol to protect the auditory system from reactive oxygen species (ROS)-mediated noise damage. Oxidative stress is mediated by ROS, which are known to cause cellular and molecular damage. Interfering with this process, using ROS inhibitors/scavengers such as antioxidants has shown promise in protecting specific systems from oxidative damage. Among the antioxidants receiving recent attention is resveratrol, an active component in red wine. Study design and setting Ten Fischer rats were used for this study. The experimental group (n = 5) received 7 weeks of resveratrol treatment (430/microg/kg/day), by gavage, and the control group (n = 5) received normal saline solution by gavage. Baseline auditory brainstem responses (3, 6, 9, 12 and 18 kHz) were determined for both groups. After 21 days, animals were exposed to noise (105 dB, 4500 to 9000 Hz for 24 hours). Postnoise auditory brainstem responses were assessed at 4 recovery time points: immediate, at 3 days, 7 days, and 4 weeks after noise exposure. RESULTS: Results demonstrate that the resveratrol group showed reduced threshold shifts compared with the control group after noise exposure. These shifts were significantly different between groups at 6 and 9 kHz (P < 0.05), corresponding to the region most represented by the frequency of the traumatic noise.Conclusion/significance Initial studies in our laboratory as well as other investigators have shown the importance of specific antioxidant therapy in the prevention of ischemic, noise, and age related hearing loss. The current study demonstrates a protective effect of resveratrol on noise-induced hearing loss.
Asunto(s)
Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Pérdida Auditiva Provocada por Ruido/complicaciones , Pérdida Auditiva Provocada por Ruido/etiología , Pérdida Auditiva Provocada por Ruido/prevención & control , Estilbenos/farmacología , Estilbenos/uso terapéutico , Animales , Umbral Auditivo/efectos de los fármacos , Cóclea/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva Provocada por Ruido/diagnóstico , Masculino , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Endogámicas F344 , Especies Reactivas de Oxígeno/metabolismo , ResveratrolRESUMEN
OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.