Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity

2012 ◽  
Vol 126 (11) ◽  
pp. 1091-1096 ◽  
Author(s):  
M Topdag ◽  
M Iseri ◽  
E Gelenli ◽  
M Yardimoglu ◽  
Y Yazir ◽  
...  

AbstractObjective:This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals.Material and methods:This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats.Results:Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p < 0.05). Although piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05).Conclusion:Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

2020 ◽  
Vol 131 ◽  
pp. 109861 ◽  
Author(s):  
David B. Behrman ◽  
Jessica L. Bishop ◽  
Jeremy Godsell ◽  
Brian Shirley ◽  
Sarah Storey ◽  
...  

2003 ◽  
Vol 14 (10) ◽  
pp. 556-562 ◽  
Author(s):  
Susan A. Small ◽  
David R. Stapells

Behavioral thresholds were measured from 31 adults with normal hearing for 500, 1000, 2000, and 4000 Hz brief tones presented using a B-71 bone oscillator. Three occlusion conditions were assessed: ears unoccluded, one ear occluded, and both ears occluded. Mean threshold force levels were 67, 54, 49, and 41 dB re:1μN peak-to-peak equivalent in the unoccluded condition for 500, 1000, 2000, and 4000 Hz, respectively (corrected for air-conduction pure-tone thresholds). A significant occlusion effect was observed for 500 and 1000 Hz stimuli. These thresholds may be used as the 0 dB nHL (normalhearing level) for brief-tone bone-conduction stimuli for auditory brainstem response testing.


2009 ◽  
Vol 201 (3) ◽  
pp. 397-406 ◽  
Author(s):  
Rusana Simonoska ◽  
Annika E Stenberg ◽  
Maoli Duan ◽  
Konstantin Yakimchuk ◽  
Anders Fridberger ◽  
...  

There are well known differences between males and females in hearing. In the present study, the role of estrogen receptor-β (ER-β; listed as ESR2 in the MGI Database) in hearing was investigated by comparing hearing and morphology of the inner ear in ER-β knock-out mice (ER-β−/−) with that of wild-type (WT) littermates. Hearing was analyzed with auditory brainstem response audiometry at 3 and 12 months. The ER-β−/− mice were deaf at 1 year of age, and the morphological analysis showed absence of hair cells and loss of the whole organ of Corti initiated in the basal turn of the cochlea. Furthermore, in ER-β−/−, but not in WT mice, the spiral ganglion was lacking many of its neurons. Immunostaining showed the presence of both ER-α (listed as ESR1 in the MGI Database) and ER-β in the nuclei of some neurons in the inner ear in WT mice, but no ER-β was found in the ER-β−/− mice as expected. ER-α staining was predominant in the nuclei of large neurons and ER-β in nuclei of small neurons and fibroblasts. These results reveal that both ERs are present in the inner ear at specific localizations suggesting subtype-specific functions. It is concluded that ER-β is important for the prevention of age-related hearing loss. These findings strengthen the hypothesis that estrogen has a direct effect on hearing functions.


2021 ◽  
Author(s):  
Yazhi Xing ◽  
Jia Fang ◽  
Zhuangzhuang Li ◽  
Mingxian Li ◽  
Chengqi Liu ◽  
...  

Abstract Background In aminoglycoside-induced hearing loss, damage to spiral ganglion neurons (SGNs) accelerates gradually after the acute outer hair cell death, accompanied by macrophage infiltration and cytokine release. Pyroptosis plays a critical role in neurodegenerative diseases. Here, we explored the potential role of pyroptosis in SGN degeneration. Methods C57BL/6J mice were randomly divided into a kanamycin plus furosemide group and saline control group. Auditory functions were evaluated by auditory brainstem response tests conducted before treatment and at 1, 5, 15, and 30 days after treatment. HCs and SGNs were assessed for morphological alterations. SGNs were subjected to RNA sequencing and mRNA and protein analyses of NLRP3 inflammasome-related molecules. Macrophage activation was evaluated based on morphological and mRNA alterations. The effect of NLRP3 inhibition on SGN survival after kanamycin treatment was evaluated in organ explant cultures treated with Mcc950, a specific inhibitor of the NLRP3 inflammasome. Results Kanamycin and furosemide administration led to irreversible deterioration of the auditory brainstem response threshold, accompanied by acute loss of outer hair cells and gradually progressive loss of inner hair cells. SGNs showed a progressive decrease in quantity, as well as swelling and membrane rupture, at 15 and 30 days. RNA sequencing of SGNs showed that inflammation and immune-related responses were significantly upregulated, as was the expression of the inflammasome-related gene NLRP3. During 30 days of kanamycin exposure, the canonical pyroptosis pathway was constantly activated in SGNs. Activation and infiltration of microglia-like cells/macrophages, and increased production of cytokines, hallmarks of neuroinflammation, were also observed. Mcc950 significantly ameliorated SGN degeneration by inhibiting NLRP3 expression and promoting release of interleukins 1β and 18. Conclusions Pyroptosis causes cell death during aminoglycoside-induced SGN degeneration. Activation of the NLRP3 inflammasome leads to a cascade of inflammatory events in SGNs. Inhibition of the NLRP3 inflammasome significantly alleviates SGN damage, suggesting that it could serve as a new molecular target for the treatment of aminoglycoside-induced SGN degeneration.


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