RESUMEN
Age-related hearing loss (AHL) or presbycusis is steadily increasing due to the overall aging of the Chinese population. Traditional Chinese medicine (TCM) has long been used to prevent and treat deafness, but its effectiveness and mechanism of action are still uncertain. The present study tested a TCM preparation called "Jian Er" in a mouse model of prebycusis.
RESUMEN
Objective To observe decreased hearing in aged C57BL/6J mice, and to study pro- tective effects of Jian' erji ( JEJ ) for age-related hearing loss (AHL) and its possible mechanism. Methods Totally 36 C57BL/6J mice were randomly divided into four groups, i.e., the normal control group (n =6) , the AHL control group (n =12) , the high dose JEJ group (n =12) , the low dose JEJ group (n =6). Mice in the normal control group drank tap water from ablactation till 2 months old. Mice in the AHL control group drank tap water from ablactation till 7 months old. Mice in high and low dose JEJ groups drank JEJ at the daily dose of 3. 65 g/kg and 0. 91 g/kg respectively from ablactation till 7 months old. Six mice were selected from each group for auditory brainstem response (ABR) using brainstem evoked potentiometer on the day of ending the test. The cochlear tissue, auditory cortex, and liver were immediately collected from 6 mice of the high dose JEJ group and 6 of the AHL control group at the same ages. Contents of malondialdehyde (MDA) , end product of lipid peroxidation were detected by UV spectrophotometer using MDA coomassie blue kit. Results ABR thresholds evoked by short-pure tone from 4 to 48 KHz were in the normal range of 2 months old mice in the normal control group. Compared with 2 months old mice in the normal control group, ABR thresholds were significantly elevated in 7 months old mice of the AHL control group (P <0. 05). Significant differences also existed in ABR thresholds from 8 to 48 KHz in the high dose JEJ group (P <0. 05). Compared with 7 months old mice of the AHL control group, MDA contents in cochlear tissue, auditory cortex, and liver were obviously reduced in the high dose JEJ group (P <0. 01). Conclusions C57BL/6J mice showed significant symptoms of AHL in high frequency range at 7 months old. Daily drinking of high dose JEJ could significantly delay the occurrence and progress of AHL. Its protection might be related to antioxidant effects JEJ contained.
Asunto(s)
Medicamentos Herbarios Chinos , Potenciales Evocados Auditivos del Tronco Encefálico , Presbiacusia , Animales , Cóclea , Medicamentos Herbarios Chinos/farmacología , Ratones , Ratones Endogámicos C57BL , Presbiacusia/prevención & controlRESUMEN
Systemic and local changes in body temperature can have a profound effect on traumatic injuries including those to the inner ear. Therefore, we investigated the effects of acutely increasing or decreasing the temperature of the external ear canal on cisplatin-induced hearing loss. The external auditory canals of male guinea pigs were acutely irrigated with warm (44 °C), euthermic (37 °C), or cool (30 °C) water and subsequently injected with cisplatin (12 mg/kg, i.p.). Hearing was assessed by the auditory brainstem response and cochleograms were prepared to determine loss of hair cells. Ear canal irrigation with warm water potentiated cisplatin-induced hearing loss and outer hair cell loss whereas cool ear canal irrigation showed significant protection from cisplatin-induced hearing loss and outer hair cell loss. These results suggest that non-invasive cool water ear canal irrigation may be highly effective clinical procedure for protecting against cisplatin-induced hearing loss.
Asunto(s)
Regulación de la Temperatura Corporal , Cisplatino , Conducto Auditivo Externo/fisiopatología , Pérdida Auditiva/prevención & control , Hipotermia Inducida , Irrigación Terapéutica/métodos , Animales , Umbral Auditivo , Cóclea/fisiopatología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico , Cobayas , Células Ciliadas Auditivas Externas/patología , Audición , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/patología , Pérdida Auditiva/fisiopatología , Hipertermia Inducida/efectos adversos , MasculinoRESUMEN
Poorer hearing in the presence of background noise is a significant problem for the hearing impaired. Ototoxic drugs, ageing, and noise exposure can damage the sensory hair cells of the inner ear that are essential for normal hearing sensitivity. The relationship between outer hair cell (OHC) loss and progressively poorer hearing sensitivity in quiet or in competing background noise is supported by a number of human and animal studies. In contrast, the effect of moderate inner hair cell (IHC) loss or dysfunction shows almost no impact on behavioral measures of hearing sensitivity in quiet, when OHCs remain intact, but the relationship between selective IHC loss and hearing in noise remains relatively unknown. Here, a moderately high dose of carboplatin (75 mg/kg) that produced IHC loss in chinchillas ranging from 40 to 80 % had little effect on thresholds in quiet. However, when tested in the presence of competing broadband (BBN) or narrowband noise (NBN), thresholds increased significantly. IHC loss >60 % increased signal-to-noise ratios (SNRs) for tones (500-11,300 Hz) in competing BBN by 5-10 dB and broadened the masking function under NBN. These data suggest that IHC loss or dysfunction may play a significant role in listening in noise independent of OHC integrity and that these deficits may be present even when thresholds in quiet are within normal limits.
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Células Ciliadas Auditivas Internas/fisiología , Células Ciliadas Auditivas Externas/fisiología , Pérdida Auditiva Provocada por Ruido/etiología , Animales , Umbral Auditivo , Carboplatino/toxicidad , Chinchilla , Células Ciliadas Auditivas Internas/efectos de los fármacos , Masculino , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
Noise trauma, aging, and ototoxicity preferentially damage the outer hair cells of the inner ear, leading to increased hearing thresholds and poorer frequency resolution. Whereas outer hair cells make synaptic connections with less than 10% of afferent auditory nerve fibers (type-II), inner hair cells make connections with over 90% of afferents (type-I). Despite these extensive connections, little is known about how selective inner hair cell loss impacts hearing. In chinchillas, moderate to high doses of the anticancer compound carboplatin produce selective inner hair cell and type-I afferent loss with little to no effect on outer hair cells. To determine the effects of carboplatin-induced inner hair cell loss on the most widely used clinical measure of hearing, the audiogram, pure-tone thresholds were determined behaviorally before and after 75 mg/kg carboplatin. Following carboplatin treatment, small effects on audiometric thresholds were observed even with extensive inner hair cell losses that exceed 80%. These results suggest that conventional audiometry is insensitive to inner hair cell loss and that only small populations of inner hair cells appear to be necessary for detecting tonal stimuli in a quiet background.
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Audiometría de Tonos Puros , Carboplatino/efectos adversos , Células Ciliadas Auditivas Internas/efectos de los fármacos , Estimulación Acústica , Animales , Antineoplásicos/efectos adversos , Umbral Auditivo/efectos de los fármacos , Umbral Auditivo/fisiología , Chinchilla , Cóclea/efectos de los fármacos , Cóclea/patología , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Células Ciliadas Auditivas Externas/efectos de los fármacos , Audición/fisiología , Masculino , Psicofísica , Células Receptoras Sensoriales/patologíaRESUMEN
Inbred strain variants of the Cdh23 gene have been shown to influence the onset and progression of age-related hearing loss (AHL) in mice. In linkage backcrosses, the recessive Cdh23 allele (ahl) of the C57BL/6J strain, when homozygous, confers increased susceptibility to AHL, while the dominant allele (Ahl+) of the CBA/CaJ strain confers resistance. To determine the isolated effects of these alleles on different strain backgrounds, we produced the reciprocal congenic strains B6.CBACa-Cdh23(Ahl)(+) and CBACa.B6-Cdh23(ahl) and tested 15-30 mice from each for hearing loss progression. ABR thresholds for 8 kHz, 16 kHz, and 32 kHz pure-tone stimuli were measured at 3, 6, 9, 12, 15 and 18 months of age and compared with age-matched mice of the C57BL/6J and CBA/CaJ parental strains. Mice of the C57BL/6N strain, which is the source of embryonic stem cells for the large International Knockout Mouse Consortium, were also tested for comparisons with C57BL/6J mice. Mice of the C57BL/6J and C57BL/6N strains exhibited identical hearing loss profiles: their 32 kHz ABR thresholds were significantly higher than those of CBA/CaJ and congenic strain mice by 6 months of age, and their 16 kHz thresholds were significantly higher by 12 months. Thresholds of the CBA/CaJ, the B6.CBACa-Cdh23(Ahl)(+), and the CBACa.B6-Cdh23(ahl) strain mice differed little from one another and only slightly increased throughout the 18-month test period. Hearing loss, which corresponded well with cochlear hair cell loss, was most profound in the C57BL/6J and C57BL/6NJ strains. These results indicate that the CBA/CaJ-derived Cdh23(Ahl)(+) allele dramatically lessens hearing loss and hair cell death in an otherwise C57BL/6J genetic background, but that the C57BL/6J-derived Cdh23(ahl) allele has little effect on hearing loss in an otherwise CBA/CaJ background. We conclude that although Cdh23(ahl) homozygosity is necessary, it is not by itself sufficient to account for the accelerated hearing loss of C57BL/6J mice.
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Cadherinas/genética , Polimorfismo de Nucleótido Simple , Presbiacusia/genética , Estimulación Acústica , Factores de Edad , Envejecimiento , Animales , Audiometría de Tonos Puros , Umbral Auditivo , Cadherinas/metabolismo , Cóclea/metabolismo , Cóclea/patología , Cóclea/fisiopatología , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Predisposición Genética a la Enfermedad , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Masculino , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , Fenotipo , Presbiacusia/metabolismo , Presbiacusia/patología , Presbiacusia/fisiopatología , Especificidad de la EspecieRESUMEN
OBJECTIVE: To study the effects of Erlong Zuoci Pill (, ELZCP) and its disassembled: prescriptions on gentamicin (GM)-induced ototoxicity model in vitro. METHODS: After the spiral organ of cochleae: of newborn mice (postnatal days: 2-3) cultured for 24 h, GM alone or combined with water extracting-alcohol precipitating solution of ELZCP or with its disassembled prescriptions was added. Hair cells were observed under a fluorescence microscope after TRITC-phalloidin staining, and the cochlear hair cell loss rate was calculated by counting the whole cochlear hair cells and analyzed by whole cochlear hair cells analyzing software. RESULTS: GM induced cochlear outer hair cells (OHCs) and inner hair cells (IHCs) injuries in a dose-dependent manner, and they were significantly different as compared with those in the normal control group (P<0.05, P<0.01). ELZCP at the concentration of 0.003-3 mg/mL could decrease the hair cells loss induced by the 0.3 mmol/L GM (P<0.05, P<0.01), the effects was in a dose-dependent manner, and the concentration of 0.3 mg/mL showed the optimal protective effect. For the ELZCP disassembled prescriptions, Liuwei-Dihuang could decrease OHC loss rate than that in the 0.3 mmol/L GM model group (P<0.05), but the OHC loss rate was still higher than that in the ELZCP group (P<0.01), which indicated that the protective effect of hair cells by Liuwei-Dihuang was not better than that of ELZCP. Poria decreased OHC loss rate from 72.1 % +/-3.7 % to 58.8 %+/- 8.2 % (P<0.05). CONCLUSIONS: ELZCP could play a role in antagonizing the injury of cochlear hair cells induced by GM ototoxicity,: and its disassembled prescriptions, Liuwei-Dihuang was the main component to protect the cochlear hair cells from GM-induced ototoxicity, and Magnetitum combined with Radix Bupleurui could strengthen the action of the whole prescription; Poria could reduce GM-induced OHC loss.
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Medicamentos Herbarios Chinos/farmacología , Gentamicinas/toxicidad , Órgano Espiral/efectos de los fármacos , Órgano Espiral/patología , Prescripciones , Animales , Relación Dosis-Respuesta a Droga , Células Ciliadas Auditivas Internas/efectos de los fármacos , Células Ciliadas Auditivas Internas/patología , Células Ciliadas Auditivas Externas/efectos de los fármacos , Células Ciliadas Auditivas Externas/patología , Ratones , ComprimidosRESUMEN
Gonadectomized and intact adult C57BL/6J (B6) mice of both sexes were exposed for 12h nightly to an augmented acoustic environment (AAE): repetitive bursts of a 70dB SPL noise band. The high-frequency AAE (HAAE) was a half-octave band centered at 20kHz; the low-frequency AAE (LAAE) was a 2-8kHz band. The effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (a trait of B6 mice) were evaluated by obtaining auditory brainstem response (ABR) thresholds at ages 3-, 6-, and 9-months. At 9-months of age, hair cell counts (cytocochleograms) were obtained, and morphometric measures of the anteroventral cochlear nucleus (AVCN) were obtained. LAAE treatment caused elevation in ABR thresholds (8-24kHz), with the highest thresholds occurring in intact females. LAAE treatment caused some loss of outer hair cells in the basal half of the cochlea (in addition to losses normally occurring in B6 mice), with intact females losing more cells than intact males. The loss of AVCN neurons and shrinkage of tissue volume that typically occur in 9-month-old B6 mice was lessened by LAAE treatment in intact (but not gonadectomized) male mice, whereas the degenerative changes were exacerbated in intact (but not gonadectomized) females. These LAAE effects were prominent in, but not restricted to, the tonotopic low-frequency (ventral) AVCN. HAAE treatment resulted in some loss of neurons in the high-frequency (dorsal) AVCN. In general, LAAE treatment plus male gonadal hormones (intact males) had an ameliorative effect whereas HAAE or LAAE treatment plus ovarian hormones (intact females) had a negative effect on age-related changes in the B6 auditory system.
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Estimulación Acústica/métodos , Vías Auditivas/patología , Umbral Auditivo , Cóclea/patología , Núcleo Coclear/patología , Potenciales Evocados Auditivos del Tronco Encefálico , Hormonas Esteroides Gonadales/metabolismo , Pérdida Auditiva/patología , Factores de Edad , Envejecimiento/patología , Animales , Vías Auditivas/metabolismo , Recuento de Células , Cóclea/metabolismo , Núcleo Coclear/metabolismo , Ambiente , Femenino , Células Ciliadas Auditivas Internas/patología , Células Ciliadas Auditivas Externas/patología , Pérdida Auditiva/genética , Pérdida Auditiva/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/patología , Orquiectomía , Ovariectomía , Factores SexualesRESUMEN
Vitamin C (ascorbate) is a water-soluble, low molecular weight antioxidant that works in conjunction with glutathione and other cellular antioxidants, and is effective against a variety of reactive oxygen species, including superoxide and hydroxyl radicals that have been implicated in the etiology of noise-induced hearing loss (NIHL). Whereas most animals can manufacture their own vitamin C, humans and a few other mammals such as guinea pigs lack the terminal enzyme for vitamin C synthesis and must obtain it from dietary sources. To determine if susceptibility to NIHL could be influenced by manipulating dietary levels of vitamin C, albino guinea pigs were raised for 35 days on a diet with normal, supplemented or deficient levels of ascorbate, then exposed to 4 kHz octave band noise at 114 dB SPL for 6 h to induce permanent threshold shifts (PTS) of the scalp-recorded auditory brainstem response. Animals that received the highest levels of dietary ascorbate developed significantly less PTS for click stimuli and 4, 8, 12, and 16 kHz tones than animals on normal and deficient diets. Outer hair cell loss was minimal in all groups after noise exposure, but permanent damage to stereocilia were observed in noise-exposed ears. The results support the hypothesis that dietary factors influence individual susceptibility to hearing loss, and suggest that high levels of vitamin C may be beneficial in reducing susceptibility to NIHL.
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Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Pérdida Auditiva Provocada por Ruido/fisiopatología , Estimulación Acústica , Análisis de Varianza , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Umbral Auditivo/efectos de los fármacos , Cilios/patología , Dieta , Potenciales Evocados Auditivos del Tronco Encefálico , Cobayas , Células Ciliadas Auditivas/patología , Pérdida Auditiva Provocada por Ruido/patología , Microscopía Electrónica de RastreoRESUMEN
Gentamicin, an aminoglycoside antibiotic, and cisplatin, a platinum-based anticancer drug, are two commonly used clinical drugs with ototoxic side effects. The ototoxicity of gentamicin and cisplatin has been linked to the production of reactive oxygen species (ROS), although the specific ROS pathways have not been identified. One ROS that might play a role in ototoxicity is the superoxide radical, which is enzymatically dismutated to molecular oxygen and hydrogen peroxide by endogenous superoxide dismutase (SOD) enzymes. M40403, a manganese-based nonpeptidyl molecule that mimics the activity of SOD, was tested for its ability to protect against gentamicin and cisplatin toxicity in cochlear organotypic cultures from neonatal C57BL/10J mice. Cultures were treated with gentamicin or cisplatin alone or in combination with M40403. M40403 alone had no effect on outer hair cell (OHC) or inner hair cell (IHC) survival at doses of 1, 5, and 10 microM, but a high dose of 30 microM reduced hair cell numbers by approximately 30%. Gentamicin alone and cisplatin alone killed OHCs and IHCs in a dose-dependent manner. The addition of M40403 to gentamicin-treated cultures significantly increased OHC and IHC survival in a dose-dependent manner, whereas M40403 failed to protect hair cells in cisplatin-treated cultures at any dose. The results suggest that the toxicity of gentamicin and cisplatin to cochlear hair cells are mediated by different pathways. Clinically, increased levels of SOD or SOD mimetics might provide significant protection against aminoglycoside ototoxicity.
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Antineoplásicos/toxicidad , Cisplatino/toxicidad , Gentamicinas/toxicidad , Células Ciliadas Auditivas/efectos de los fármacos , Compuestos Organometálicos/uso terapéutico , Animales , Antineoplásicos/antagonistas & inhibidores , Células Cultivadas , Cisplatino/antagonistas & inhibidores , Cóclea/efectos de los fármacos , Cóclea/patología , Gentamicinas/antagonistas & inhibidores , Manganeso , Ratones , Ratones Endogámicos C57BLRESUMEN
Acoustic overstimulation produces many anatomical, biochemical and physiological changes in the inner ear. However, the changes in gene expression that underlie these biological changes are poorly understood. Our approach to investigating this problem is to use gene microarrays to measure the changes in gene expression in the chinchilla inner ear following a 3 h or 6 h noise exposure (95 dB SPL, 707-1414 Hz). This noise exposure causes a temporary threshold shift (~40 dB) and a temporary reduction in distortion product otoacoustic emissions (DPOAE), but no permanent hearing loss or hair cell loss. Here, we present data showing (1) the suitability of mouse and human complementary DNA (cDNA) clones for detecting chinchilla cochlear gene transcripts, and (2) the change in cochlear gene transcripts in noise exposed chinchillas. Chinchilla cochlear transcript probes exhibited strong and discrete signals on both mouse and human cDNA filter arrays. Since the strongest hybridization occurred with mouse clones, mouse cDNA microarrays were used to study noise-induced changes in gene expression. Chinchilla cDNA probes were differentially labelled with Cy3 (control) or Cy5 (noise exposed) by random primed synthesis, hybridized to 8750 mouse cDNAs arrayed on microscope slides and analysed by laser fluorescent microscopy. Several classes of genes exhibited time-dependent up regulation of transcription, including those involved in protein synthesis, metabolism, cytoskeletal proteins, and calcium binding proteins. The results are discussed in relationship to previous studies showing noise-induced changes in structural proteins, calcium binding proteins, metabolic enzymes and membrane bound vesicles.