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Otoprotection

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https://www.readbyqxmd.com/read/28796092/oral-administration-of-clinical-stage-drug-candidate-sens-401-effectively-reduces-cisplatin-induced-hearing-loss-in-rats
#1
Mathieu Petremann, Christophe Tran Van Ba, Audrey Broussy, Charlotte Romanet, Jonas Dyhrfjeld-Johnsen
HYPOTHESIS: SENS-401, an oral clinical-stage drug, may reduce cisplatin-induced hearing loss and cochlear damage in an in vivo model. BACKGROUND: Cisplatin is commonly associated with hearing loss, causing significant learning and behavioral difficulties in the pediatric cancer population, and for which there are currently no clinical solutions. SENS-401 has previously been shown to improve acoustic trauma-induced hearing loss in vivo. METHODS: The effect of SENS-401 (R-azasetron besylate) on cisplatin IC50 values was evaluated in a panel of cisplatin-sensitive cell lines (NIH:OVCAR-3, SK-N-AS, NCI-H460, FaDu)...
August 8, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28703809/epigallocatechin-3-gallate-a-prototypic-chemopreventative-agent-for-protection-against-cisplatin-based-ototoxicity
#2
Vikrant Borse, Raheem F H Al Aameri, Kelly Sheehan, Sandeep Sheth, Tejbeer Kaur, Debashree Mukherjea, Srinivasan Tupal, Michelle Lowy, Sumana Ghosh, Asmita Dhukhwa, Puspanjali Bhatta, Leonard P Rybak, Vickram Ramkumar
Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28673569/calcium-channel-blockers-as-therapeutic-agents-for-acquired-sensorineural-hearing-loss
#3
James G Naples
Acquired sensorineural hearing loss represents a challenging clinical scenario. Currently, there are few approved therapies for treating this type of hearing loss, and diagnosis is often made after permanent damage has occurred. There are numerous etiologies for acquired hearing loss, with complex mechanisms underlying each cause. Despite these complexities, apoptosis of the structures within the inner ear, is a theme common to many forms of acquired hearing loss. Apoptosis is a calcium-dependent process, and within the inner ear, L- and T-type calcium channels are believed to contribute to calcium availability during this process...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28560432/otoprotective-effects-of-ethosuximide-in-nod-ltj-mice-with-age-related-hearing-loss
#4
Lu Sang, Tihua Zheng, Lingqian Min, Xiaolin Zhang, Xiufang Ma, Shami Entenman, Yipeng Su, Qingyin Zheng
Despite long-term efforts to elucidate the mechanisms responsible for age-related hearing loss (AHL), there is currently no available treatment strategy able to provide a cure. Apoptotic cell death, including that of hair cells and spiral ganglion neurons (SGNs) in the cochlea has been proposed to be the classic theory behind the development of AHL. As calcium signaling plays key roles in signal transduction in apoptosis, in this study, we selected ethosuximide, which is able to block T-type calcium (Ca2+ion) channels, suppressing Ca2+...
July 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28520533/a-fully-automated-high-throughput-zebrafish-behavioral-ototoxicity-assay
#5
Douglas W Todd, Rohit C Philip, Maki Niihori, Ryan A Ringle, Kelsey R Coyle, Sobia F Zehri, Leanne Zabala, Jordan A Mudery, Ross H Francis, Jeffrey J Rodriguez, Abraham Jacob
Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells...
August 2017: Zebrafish
https://www.readbyqxmd.com/read/28503132/protecting-mammalian-hair-cells-from-aminoglycoside-toxicity-assessing-phenoxybenzamine-s-potential
#6
Paromita Majumder, Paulette A Moore, Guy P Richardson, Jonathan E Gale
Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28460251/streptococcus-pneumoniae-induced-ototoxicity-in-organ-of-corti-explant-cultures
#7
Michael Perny, Magdalena Solyga, Denis Grandgirard, Marta Roccio, Stephen L Leib, Pascal Senn
Hearing loss remains the most common long-term complication of pneumococcal meningitis (PM) reported in up to 30% of survivors. Streptococcus pneumoniae have been shown to possess different ototoxic properties. Here we present a novel ex vivo experimental setup to examine in detail the pattern of hair cell loss upon exposure to different S. pneumoniae strains, therefore recapitulating pathogen derived aspects of PM-induced hearing loss. Our results show a higher susceptibility towards S. pneumoniae-induced cochlear damage for outer hair cells (OHC) compared to inner hair cells (IHC), which is consistent with in vivo data...
July 2017: Hearing Research
https://www.readbyqxmd.com/read/28448657/association-between-slc16a5-genetic-variation-and-cisplatin-induced-ototoxic-effects-in-adult-patients-with-testicular-cancer
#8
Britt I Drögemöller, Jose G Monzon, Amit P Bhavsar, Adrienne E Borrie, Beth Brooks, Galen E B Wright, Geoffrey Liu, Daniel J Renouf, Christian K Kollmannsberger, Philippe L Bedard, Folefac Aminkeng, Ursula Amstutz, Claudette A Hildebrand, Erandika P Gunaretnam, Carol Critchley, Zhuo Chen, Liam R Brunham, Michael R Hayden, Colin J D Ross, Karen A Gelmon, Bruce C Carleton
Importance: Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects. Objective: To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients...
April 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28345280/otoprotective-effects-of-mouse-nerve-growth-factor-in-dba-2j-mice-with-early-onset-progressive-hearing-loss
#9
Qingzhu Wang, Hongchun Zhao, Tihua Zheng, Wenjun Wang, Xiaolin Zhang, Andi Wang, Bo Li, Yanfei Wang, Qingyin Zheng
As it displays progressive hair-cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL), DBA/2J is an inbred mouse strain widely used in hearing research. Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth...
October 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28264554/hearing-improvement-in-a-j-mice-via-the-mouse-nerve-growth-factor
#10
Lixiang Gao, Ruli Ge, Gang Xie, Dandan Yao, Ping Li, Oumei Wang, Xiufang Ma, Fengchan Han
Objectives: To investigate the otoprotective effects of mouse nerve growth factor (mNGF) in A/J mice. Methods: The mice at postnatal day 7 (P7) were randomly separated into a mNGF treated group (mNGF group) and a distilled water (for injection) treated group (control group). The mNGF dissolved in distilled water or distilled water alone was given to the mice once every other day from P7 by intramuscular injection in the hips. The otoprotective effects of mNGF in A/J mice were observed in a time course manner...
March 8, 2017: Clinical and Experimental Otorhinolaryngology
https://www.readbyqxmd.com/read/28112219/c-myb-knockdown-increases-the-neomycin-induced-damage-to-hair-cell-like-hei-oc1-cells-in-vitro
#11
Xiaoyu Yu, Wenwen Liu, Zhaomin Fan, Fuping Qian, Daogong Zhang, Yuechen Han, Lei Xu, Gaoying Sun, Jieyu Qi, Shasha Zhang, Mingliang Tang, Jianfeng Li, Renjie Chai, Haibo Wang
c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28007648/minocycline-attenuates-noise-induced-hearing-loss-in-rats
#12
Jing Zhang, Yong-Li Song, Ke-Yong Tian, Jian-Hua Qiu
Noise-induced hearing loss (NIHL) is a serious health concern and prevention of hair cell death or therapeutic intervention at the early stage of NIHL is critical to preserve hearing. Minocycline is a semi-synthetic derivative of tetracycline and has been shown to have otoprotective effects in ototoxic drug-induced hearing impairment, however, whether minocycline can protect against NIHL has not been investigated. The present study demonstrated elevated ABR (auditory brainstem response) thresholds and outer hair cell loss following traumatic noise exposure, which was mitigated by intraperitoneal administration of minocycline (45mg/kg/d) for 5 consecutive days...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27914822/effects-of-sodium-thiosulfate-versus-observation-on-development-of-cisplatin-induced-hearing-loss-in-children-with-cancer-accl0431-a-multicentre-randomised-controlled-open-label-phase-3-trial
#13
RANDOMIZED CONTROLLED TRIAL
David R Freyer, Lu Chen, Mark D Krailo, Kristin Knight, Doojduen Villaluna, Bonnie Bliss, Brad H Pollock, Jagadeesh Ramdas, Beverly Lange, David Van Hoff, Michele L VanSoelen, John Wiernikowski, Edward A Neuwelt, Lillian Sung
BACKGROUND: Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. METHODS: ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada...
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27878601/reduction-of-permanent-hearing%C3%A2-loss-by-local-glucocorticoid-application-guinea-pigs-with-acute-acoustic-trauma
#14
M Müller, M Tisch, H Maier, H Löwenheim
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined...
January 2017: HNO
https://www.readbyqxmd.com/read/27742965/-reduction-of-permanent-hearing-loss-by-local-glucocorticoid-application-guinea-pigs-with-acute-acoustic-trauma-german-version
#15
M Müller, M Tisch, H Maier, H Löwenheim
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined...
November 2016: HNO
https://www.readbyqxmd.com/read/27669661/medical-interventions-for-the-prevention-of-platinum-induced-hearing-loss-in-children-with-cancer
#16
REVIEW
Jorrit W van As, Henk van den Berg, Elvira C van Dalen
BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. One of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the efficacy of medical interventions to prevent hearing loss and to determine possible effects of these interventions on anti-tumour efficacy, toxicities other than hearing loss and quality of life in children with cancer treated with platinum-based therapy...
September 27, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27548570/the-safety-and-tolerability-of-the-second-line-injectable-antituberculosis-drugs-in-children
#17
REVIEW
Anthony J Garcia-Prats, H Simon Schaaf, Anneke C Hesseling
A growing number of children globally are being treated for multidrug-resistant tuberculosis (MDR-TB). The second-line injectable antituberculosis medications amikacin, kanamycin and capreomycin, traditionally a mainstay of MDR-TB treatment, cause important adverse effects including permanent sensorineural hearing loss, nephrotoxicity, electrolyte abnormalities, injection pain and local injection site complications. Areas covered: To characterize the safety and tolerability of the second-line injectables in children treated for MDR-TB, we reviewed data on the mechanism of injectable associated adverse effects, risk factors for their development, and the incidence of injectable-associated adverse effects in adults and children treated for MDR-TB...
November 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27518137/serial-monitoring-of-otoacoustic-emissions-in-clinical-trials
#18
Dawn Konrad-Martin, Gayla L Poling, Laura E Dreisbach, Kelly M Reavis, Garnett P McMillan, Judi A Lapsley Miller, Lynne Marshall
The purpose of this report is to provide guidance on the use of otoacoustic emissions (OAEs) as a clinical trial outcome measure for pharmaceutical interventions developed to prevent acquired hearing loss secondary to cochlear insult. OAEs are a rapid, noninvasive measure that can be used to monitor cochlear outer hair cell function. Serial monitoring of OAEs is most clearly established for use in hearing conservation and ototoxicity monitoring programs in which they exhibit more frequent and earlier changes compared with pure-tone audiometry...
September 2016: Otology & Neurotology
https://www.readbyqxmd.com/read/27518134/guidelines-for-auditory-threshold-measurement-for-significant-threshold-shift
#19
Kathleen Campbell, Tanisha Hammill, Michael Hoffer, Jonathan Kil, Colleen Le Prell
The purpose of this article is to provide guidelines for determining a Significant Noise-Induced Threshold Shift in clinical trials involving human populations. The article reviews recommendations for the standards to be referenced for human subjects, equipment, test environment, and personnel. Additional guidelines for military populations are provided. Guidelines for the calibration of audiometers, sound booth noise levels, and immitance equipment are provided. In addition the guidance provides specific suggestions for the subjects history before study onset, and otoscopy...
September 2016: Otology & Neurotology
https://www.readbyqxmd.com/read/27487360/protective-effect-of-korean-red-ginseng-on-cisplatin-ototoxicity-is-it-effective-enough
#20
Yüksel Olgun, Günay Kırkım, Zekiye Altun, Safiye Aktaş, Efsun Kolatan, Müge Kiray, Alper Bağrıyanık, Aybüke Olgun, Deniz Çakır Kızmazoğlu, Candan Özoğul, Hülya Ellidokuz, Pınar Erçetin, Bülent Şerbetçioğlu, Osman Yılmaz, Enis Alpin Güneri
OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS: The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups...
August 2016: Journal of International Advanced Otology
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