Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

针刺防治GE对豚鼠内耳损害的实验研究

目的 观察针刺对庆大霉素（ＧＥ）耳中毒豚鼠的防治作用。方法 用脑干听觉诱发电位（ＢＡＥＰ）和组织化学方法,检测动物耳聋程度及听神经功能的变化和耳蜗毛细胞酶活性的改变。结果 电针能降低ＧＥ引起的ＢＡＥＰ反应阈的上升幅度,降低ＢＡＥＰ波峰潜伏期及波间期的延长;能保护毛细胞线粒体呼吸酶的活性,维持毛细胞溶酶体的完整性。结论 针刺能降低ＧＥ的耳毒性。保护毛细胞线粒体酶的活性,维持溶酶体的完整性,保证毛细胞     

铂类的耳毒性

铂类化合物的耳毒性具有初期症状隐匿 ,不可逆性和严重影响生活质量等特点 ,逐渐为临床医师所关注。该文对其发病情况 ,病理学改变 ,临床特征和防治措施等加以综述。     

Brief-Tone Audiometry in Persons Treated with Salicylate

The ability to integrate acoustic energy over a period of time has been measured by brief-tone audiometry on 14 young persons treated with salicylate and after the salicylate has been excreted. The investigation showed that the temporal integration can be reversible reduced by salicylate treatment, and a relation was demonstrated between the change in temporal integration and the salicylate concentration in the blood. As the test persons had had general anaesthesia, a control test was performed on seven persons. It was shown that anaesthesia does not influence temporal integration. Experimental investigations have shown that the hearing loss produced by salicylate is due to an inhibition of enzymatic systems in the cochlea

Taking into consideration the results of brief-tone audiometry and the cochlear effect of the salicylates, one must conclude that reduced cochlear function caused reduced temporal integration     

Protective role of L‐ascorbic acid,N‐acetylcysteine and apocynin on neomycin‐induced hair cell loss in Zebrafish

Hair cells are highly sensitive to environmental insults and other therapeutic drugs. The adverse effects of drugs such as aminoglycosides can cause hair cell death and lead to hearing loss and imbalance. The objective of the present study was to evaluate the protective activity of L‐ascorbic acid, N‐acetylcysteine (NAC) and apocynin on neomycin‐induced hair cell damage in zebrafish (Danio rerio) larvae at 5 days post fertilization (dpf). Results showed that the loss of hair cells within the neuromasts of the lateral lines after neomycin exposure was evidenced by a significantly lower number of neuromasts labeled with fluorescent dye FM1‐43FX observed under a microscope. Co‐administration with L‐ascorbic acid, NAC and apocynin protected neomycin‐induced hair cell loss within the neuromasts. Moreover, these three compounds reduced the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin, indicating that their antioxidant action is involved. In contrast, the neuromasts were labeled with specific fluorescent dye Texas‐red conjugated with neomycin to detect neomycin uptake. Interestingly, the uptake of neomycin into hair cells was not influenced by these three antioxidant compounds. These data imply that prevention of hair cell damage against neomycin by L‐ascorbic acid, NAC and apocynin might be associated with inhibition of excessive ROS production, but not related to modulating neomycin uptake. Our findings conclude that L‐ascorbic acid, NAC and apocynin could be used as therapeutic drugs to protect aminoglycoside‐induced listening impairment after further confirmatory studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Early Physiological and Cellular Indicators of Cisplatin-Induced Ototoxicity

Cisplatin chemotherapy often causes permanent hearing loss, which leads to a multifaceted decrease in quality of life. Identification of early cisplatin-induced cochlear damage would greatly improve clinical diagnosis and provide potential drug targets to prevent cisplatin’s ototoxicity. With improved functional and immunocytochemical assays, a recent seminal discovery revealed that synaptic loss between inner hair cells and spiral ganglion neurons is a major form of early cochlear damage induced by noise exposure or aging. This breakthrough discovery prompted the current study to determine early functional, cellular, and molecular changes for cisplatin-induced hearing loss, in part to determine if synapse injury is caused by cisplatin exposure. Cisplatin was delivered in one to three treatment cycles to both male and female mice. After the cisplatin treatment of three cycles, threshold shift was observed across frequencies tested like previous studies. After the treatment of two cycles, beside loss of outer hair cells and an increase in high-frequency hearing thresholds, a significant latency delay of auditory brainstem response wave 1 was observed, including at a frequency region where there were no changes in hearing thresholds. The wave 1 latency delay was detected as early cisplatin-induced ototoxicity after only one cycle of treatment, in which no significant threshold shift was found. In the same mice, mitochondrial loss in the base of the cochlea and declining mitochondrial morphometric health were observed. Thus, we have identified early spiral ganglion-associated functional and cellular changes after cisplatin treatment that precede significant threshold shift.     

Exosomes derived from mouse inner ear stem cells attenuate gentamicin‐induced ototoxicity in vitro through the miR‐182‐5p/FOXO3 axis

Gentamicin‐induced cochlear hair cell ototoxicity, such as oxidative stress and apoptosis, could be attenuated by mouse inner ear stem cells (IESCs). However, it is still unclear whether such protective effects could be mediated by exosomes derived from IESCs (IESCs‐ex). In the present study, HEI‐OC1 cells were exposed to gentamicin (2 mM) to establish an ototoxicity model and further treated with exosomes isolated from miR‐182‐5p transferred or non‐transferred IESCs. IESCs‐ex improved HEI‐OC1 cell viability, as assayed by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide method, and alleviated the oxidative stress response induced by the gentamicin treatment, as confirmed by measuring the malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase levels. IESCs‐ex increased relative miR‐182‐5p expression and decreased FOXO3 expression in the gentamicin‐exposed HEI‐OC1 cells. Furthermore, exosomes derived from miR‐182‐5p mimics that were pre‐treated with IESCs could increase miR‐182‐5p and Bcl‐2 expressions and decrease FOXO3 and Bax expressions in gentamicin‐exposed HEI‐OC1 cells. All of these results indicate that IESCs‐ex could attenuate gentamicin‐induced HEI‐OC1 cell apoptosis and oxidative stress through the miR‐182‐5p/FOXO3 axis.