scholarly journals Brimonidine Protects Auditory Hair Cells from in vitro-Induced Toxicity of Gentamicin

2017 ◽  
Vol 22 (3) ◽  
pp. 125-134 ◽  
Author(s):  
Maurizio Cortada ◽  
Soledad Levano ◽  
Daniel Bodmer
Keyword(s):  
Protein Expression ◽  
Protective Effect ◽  
Hair Cells ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Neuroprotective Effects ◽  
Auditory Hair Cells ◽  
Expression Levels ◽  
Ganglion Neurons

Brimonidine, an alpha-2 adrenergic receptor (α2-AR) agonist, has neuroprotective effects in the visual system and in spiral ganglion neurons. Auditory hair cells (HCs) express all 3 α2-AR subtypes, but their roles in HCs remain unknown. This study investigated the effects of brimonidine on auditory HCs that were also exposed to gentamicin, which is toxic to HCs. Organ of Corti explants were exposed to gentamicin in the presence or absence of brimonidine, and the α2-AR protein expression levels and Erk1/2 and Akt phosphorylation levels were determined. Brimonidine had a protective effect on auditory HCs against gentamicin-induced toxicity that was blocked by yohimbine. This suggested that the protective effect of brimonidine on HCs was mediated by the α2-AR. None of the treatments altered α2-AR protein expression levels, and brimonidine did not significantly change the activation levels of the Erk1/2 and Akt proteins. These observations indicated that brimonidine, acting directly via α2-AR, protects HCs from gentamicin-induced toxicity. Therefore, brimonidine shows potential for preventing or treating sensorineural hearing loss.

scholarly journals Caffeine Induces Autophagy and Apoptosis in Auditory Hair Cells via the SGK1/HIF-1α Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaomin Tang ◽  
Yuxuan Sun ◽  
Chenyu Xu ◽  
Xiaotao Guo ◽  
Jiaqiang Sun ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Spiral Ganglion Neurons ◽  
Auditory Hair Cells ◽  
Qrt Pcr ◽  
Ganglion Neurons

Caffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. To confirm our observations in vitro, we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. We verified the interaction between SGK1 and HIF-1α by co-IP. To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl2 was used as an inducer of HIF-1α. Western blot analysis suggested that GSK650394 and CoCl2 relieved the caffeine-induced apoptosis and autophagy. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.

Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro

2015 ◽  
Vol 20 (6) ◽  
pp. 360-369 ◽  
Author(s):  
Andrea Glutz ◽  
Katharina Leitmeyer ◽  
Cristian Setz ◽  
Yves Brand ◽  
Daniel Bodmer
Keyword(s):  
Hair Cells ◽  
Apoptotic Cell ◽  
Mammalian Target Of Rapamycin ◽  
Spiral Ganglion ◽  
Oxygen Species ◽  
Antidiabetic Drug ◽  
Auditory Hair Cells ◽  
Amp Activated Protein Kinase ◽  
Toxicity In Vitro

Metformin is a commonly used antidiabetic drug. It has been shown that this drug activates the AMP-activated protein kinase, which inhibits downstream the mammalian target of rapamycin. In addition, several studies indicate that metformin reduces intracellular reactive oxygen species. Our data, using an in vitro rat model, indicate that metformin is able to protect auditory hair cells (HCs) from gentamicin-induced apoptotic cell death. Moreover, metformin has no toxic effect on spiral ganglion neuronal survival or outgrowth in vitro. These results suggest a protective effect of metformin on auditory HC survival in gentamicin-induced HC loss in vitro.

scholarly journals Resveratrol Protects Auditory Hair Cells from Gentamicin Toxicity

2008 ◽  
Vol 87 (10) ◽  
pp. 570-573 ◽  
Author(s):  
Sharouz Bonabi ◽  
Antje Caelers ◽  
Arianne Monge ◽  
Alex Huber ◽  
Daniel Bodmer
Keyword(s):  
Hair Cells ◽  
Organ Of Corti ◽  
Sprague Dawley ◽  
Auditory Hair Cells ◽  
Sprague Dawley Rats ◽  
Scavenger Activity ◽  
Ros Scavenger ◽  
And Control ◽  
Toxicity In Vitro

Resveratrol is a naturally occurring polyphenol that is synthesized by a variety of plant species. It is abundant in grapes and grape products (e.g., red wine). Resveratrol has demonstrated reactive oxygen species (ROS) scavenger activity, and it has been linked to nuclear factor-kappa B (NF-κB) activity. We recently demonstrated that NF-κB is important to the survival of immature mammalian hair cells. Therefore, we undertook an in vitro experiment to determine if resveratrol is able to exert some protective influence against gentamicin-induced damage to and death of auditory hair cells. To accomplish this, we dissected the organ of Corti (OC) from newborn Sprague-Dawley rats and cultured the OCs in medium overnight for recovery. We treated two groups of OC explants with different concentrations of resveratrol plus gentamicin for 24 hours; for comparison and control purposes, we also treated a group of explants with gentamicin only and we left a group untreated. We found that resveratrol in both concentrations had a moderate but statistically significant protective effect against gentamicin-induced toxicity in vitro.

scholarly journals Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 409 ◽  
Author(s):  
Mi-Jin Choi ◽  
Hyunsook Kang ◽  
Yun Yeong Lee ◽  
Oak-Sung Choo ◽  
Jeong Hun Jang ◽  
...  
Keyword(s):  
Cell Death ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Auditory Brainstem ◽  
Sprague Dawley ◽  
Western Blots ◽  
Brainstem Response ◽  
Ganglion Neurons

Cisplatin-induced early-onset ototoxicity is linked to hearing loss. The mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase (RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in vitro and in vivo. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p.) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H & E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. Inhibitor experiments with necrostatin 1 (Nec-1) and Z-VAD were also performed in HEI-OC1 cell line. H&E stains revealed that the necroptotic changes were increased in the organ of Corti (OC) and spiral ganglion neurons (SGNs). Moreover, immunohistochemistry and western blot analysis showed that cisplatin treatment increased the protein levels of RIP3 in both OCs and SGNs. The treatment of Nec-1, a selective RIP1 inhibitor, resulted in markedly suppression of cisplatin-induced cell death in HEI-OC1 cells, whereas Z-VAD treatment did not change the cisplatin-induced cell death. Our results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

Brain-derived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss

1998 ◽  
Vol 119 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Hinrich Staecker ◽  
Ramin Gabaizadeh ◽  
Howard Federoff ◽  
Thomas R. Van De Water
Keyword(s):  
Hair Cells ◽  
Neurotrophic Factor ◽  
Spiral Ganglion ◽  
Brain Derived Neurotrophic Factor ◽  
In Vivo Studies ◽  
Auditory Neurons ◽  
Secondary Degeneration ◽  
Auditory Hair Cells ◽  
Neurotrophin 3

Destruction of auditory hair cells results in the secondary degeneration of auditory neurons. This is because of the loss of neurotrophic factor support from the auditory hair cells, namely neurotrophin 3, which is normally produced by the inner hair cells. Both in vitro and in vivo studies have shown that delivery of either neurotrophin 3 or brain-derived neurotrophic factor to these neurons can replace the trophic support supplied by the hair cells and prevent their degeneration. To prevent the degeneration of auditory neurons that occurs after neomycin destruction of the auditory hair cells we used a replication defective herpes simplex-1 vector (HSVbdnflac) to transfect the gene for brain-derived neurotrophic factor into the damaged spiral ganglion. Four weeks after the HSVbdnflac therapy we were able to detect stable functional production of brain-derived neurotrophic factor that supported the survival of auditory neurons and prevented the loss of these neurons because of trophic factor deprivation-induced apoptosis. (Otolaryngol Head Neck Surg 1998;119:7–13.)

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