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aminoglycoside ototoxicity

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https://www.readbyqxmd.com/read/29218724/genetic-disruption-of-fractalkine-signaling-leads-to-enhanced-loss-of-cochlear-afferents-following-ototoxic-or-acoustic-injury
#1
Tejbeer Kaur, Kevin K Ohlemiller, Mark E Warchol
Cochlear hair cells are vulnerable to a variety of insults like acoustic trauma and ototoxic drugs. Such injury can also lead to degeneration of spiral ganglion neurons (SGNs), but this occurs over a period of months to years. Neuronal survival is necessary for the proper function of cochlear prosthetics, therefore it is of great interest to understand the mechanisms that regulate neuronal survival in deaf ears. We have recently demonstrated that selective hair cell ablation is sufficient to attract leukocytes into the spiral ganglion (SG), and that fractalkine signaling plays a role in macrophage recruitment and in the survival of auditory neurons...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29214897/ss-31-peptide-enables-mitochondrial-targeting-drug-delivery-a-promising-therapeutic-alteration-to-prevent-hair-cell-damage-from-aminoglycosides
#2
Xiao Kuang, Shuang Zhou, Weiling Guo, Zhenjie Wang, Yanhui Sun, Hongzhuo Liu
Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a key role in that cellular dysfunction for which no proven effective therapies against oto-toxicities exist. Therefore, the aim of the present study was to develop a new mitochondrial targeting drug delivery system (DDS) that provided improved protection from gentamicin. Particularly, SS-31 peptide-conjugated geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were constructed successfully via emulsion-solvent evaporation method...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29213239/dynamic-editome-of-zebrafish-under-aminoglycosides-treatment-and-its-potential-involvement-in-ototoxicity
#3
Sijia Yan, Yulan Lu, Lin He, Xinzhi Zhao, Lihua Wu, Huizhong Zhu, Menglin Jiang, Yu Su, Wei Cao, Weidong Tian, Qinghe Xing
RNA editing is an important co- and post-transcriptional event that generates RNA and protein diversity. Aminoglycosides are a group of bactericidal antibiotics and a mainstay of antimicrobial therapy for several life-threatening infections. However, aminoglycosides can induce ototoxicity, resulting in damage to the organs responsible for hearing and balance. At low concentrations, aminoglycosides can bind to many RNA sequences and critically influence RNA editing. We used a bioinformatics approach to investigate the effect of aminoglycosides on global mRNA editing events to gain insight into the interactions between mRNA editing and aminoglycoside ototoxicity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29194212/evaluation-of-mitoquinone-for-protecting-against-amikacin-induced-ototoxicity-in-guinea-pigs
#4
Carolyn O Dirain, Maria Raye Ann V Ng, Bailey Milne-Davies, Jerin K Joseph, Patrick J Antonelli
HYPOTHESIS: Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs. BACKGROUND: MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus, MitoQ is a promising therapeutic approach for protecting against amikacin-induced ototoxicity. METHODS: Both oral and subcutaneous administrations of MitoQ were tested. Amikacin-treated guinea pigs (n = 12-18 per group) received water alone (control) or MitoQ 30 mg/l-supplemented drinking water; or injected subcutaneously with 3 to 5 mg/kg MitoQ or saline (control)...
November 29, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/29173064/pharmacogenetics-of-drug-induced-ototoxicity-caused-by-aminoglycosides-and-cisplatin
#5
Claudia Lanvers-Kaminsky, Giuliano Ciarimboli
Aminoglycosides and the anticancer drug cisplatin can cause permanent hearing loss, which impacts patients' quality of life and results in considerable subsequent costs. Since patients' individual susceptibility to aminoglycoside- and cisplatin-induced ototoxicity varies considerably, strategies are needed to identify patients at risk, who may require alternative treatments or specific protection strategies. For both drugs, various genetic variants were linked to an increased or decreased risk for ototoxicity...
November 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29160511/the-importance-of-audiometric-monitoring-in-patients-with-multidrug-resistant-tuberculosis
#6
Karla Anacleto de Vasconcelos, Silvana Maria Monte Coelho Frota, Antonio Ruffino-Netto, Afrânio Lineu Kritski
INTRODUCTION: A total of 771 cases of multidrug-resistant tuberculosis (MDR-TB) were reported in Brazil in 2014. Treatment of MDR-TB with aminoglycosides can produce serious side effects such as permanent and irreversible hearing loss, which occurs in 5-64% of cases, and severely compromise patient quality of life. The goal of this research was to evaluate auditory and vestibular side effects in patients treated for MDR-TB and to identify associations between these complaints and the type of aminoglycoside used...
September 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29134476/aminoglycoside-damage-and-hair-cell-regeneration-in-the-chicken-utricle
#7
Mirko Scheibinger, Daniel C Ellwanger, C Eduardo Corrales, Jennifer S Stone, Stefan Heller
In this study, we present a systematic characterization of hair cell loss and regeneration in the chicken utricle in vivo. A single unilateral surgical delivery of streptomycin caused robust decline of hair cell numbers in striolar as well as extrastriolar regions, which in the striola was detected very early, 6 h post-insult. During the initial 12 h of damage response, we observed global repression of DNA replication, in contrast to the natural, mitotic hair cell production in undamaged control utricles...
November 13, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/29114207/histone-deacetylase-inhibitors-are-protective-in-acute-but-not-in-chronic-models-of-ototoxicity
#8
Chao-Hui Yang, Zhiqi Liu, Deanna Dong, Jochen Schacht, Dev Arya, Su-Hua Sha
Previous studies have reported that modification of histones alters aminoglycoside-induced hair cell death and hearing loss. In this study, we investigated three FDA-approved histone deacetylase (HDAC) inhibitors (vorinostat/SAHA, belinostat, and panobinostat) as protectants against aminoglycoside-induced ototoxicity in murine cochlear explants and in vivo in both guinea pigs and CBA/J mice. Individually, all three HDAC inhibitors reduced gentamicin (GM)-induced hair cell loss in a dose-dependent fashion in explants...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29105116/a-mitochondrial-targeting-tetrapeptide-bendavia-protects-lateral-line-hair-cells-from-gentamicin-exposure
#9
Xiao Kuang, Yanhui Sun, Zhenjie Wang, Shuang Zhou, Hongzhuo Liu
The hearing loss induced by aminoglycosides is caused by the permanent loss of mechanosensory hair cells of the inner ear. The aim of the present study is therefore to evaluate the protective effect of Bendavia, a novel antioxidant, on gentamicin-induced hair cell damage in zebrafish lateral lines. The results demonstrated the pretreatment of Bendavia exhibited dose-dependent protection against gentamicin in both acute and chronic exposure. We found that Bendavia at 150 μm conferred optimal protection from either acute or chronic exposure with ototoxin...
November 3, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29097487/long-term-protective-effect-of-n-acetylcysteine-against-amikacin-induced-ototoxicity-in-end-stage-renal-disease-a-randomized-trial
#10
Alperen Vural, Ismail Kocyigit, Furkan Şan, Eray Eroglu, İbrahim Ketenci, Aydin Unal, Bulent Tokgoz, Yaşar Ünlü
BACKGROUND: The aim of the study is to evaluate the long-term protective effect of N-acetylcysteine (NAC), an antioxidant agent, against aminoglycoside (AG)-induced ototoxicity. METHODS: A total of 40 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and having their first peritonitis attacks and planned to be treated with AGs were enrolled in the study. They were randomized into 2 groups: 1 group received additional NAC and the other did not. All patients underwent hearing tests with pure tone audiometry (PTA) after the diagnosis, at 1 month and 12 months and at the same time the tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured...
November 2, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/29093665/pi3k-and-inhibitor-of-apoptosis-proteins-modulate-gentamicin-induced-hair-cell-death-in-the-zebrafish-lateral-line
#11
Heather Wiedenhoft, Lauren Hayashi, Allison B Coffin
Inner ear hair cell death leads to sensorineural hearing loss and can be a direct consequence of aminoglycoside antibiotic treatment. Aminoglycosides such as gentamicin are effective therapy for serious Gram-negative bacterial infections such as some forms of meningitis, pneumonia, and sepsis. Aminoglycosides enter hair cells through mechanotransduction channels at the apical end of hair bundles and initiate intrinsic cell death cascades, but the precise cell signaling that leads to hair cell death is incompletely understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29093664/towards-the-prevention-of-aminoglycoside-related-hearing-loss
#12
REVIEW
Mary E O'Sullivan, Adela Perez, Randy Lin, Autefeh Sajjadi, Anthony J Ricci, Alan G Cheng
Aminoglycosides are potent antibiotics deployed worldwide despite their known side-effect of sensorineural hearing loss. The main etiology of this sensory deficit is death of inner ear sensory hair cells selectively triggered by aminoglycosides. For decades, research has sought to unravel the molecular events mediating sensory cell demise, emphasizing the roles of reactive oxygen species and their potentials as therapeutic targets. Studies in recent years have revealed candidate transport pathways including the mechanotransducer channel for drug entry into sensory cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29093662/tmc2-modifies-permeation-properties-of-the-mechanoelectrical-transducer-channel-in-early-postnatal-mouse-cochlear-outer-hair-cells
#13
Laura F Corns, Jing-Yi Jeng, Guy P Richardson, Corné J Kros, Walter Marcotti
The ability of cochlear hair cells to convert sound into receptor potentials relies on the mechanoelectrical transducer (MET) channels present in their stereociliary bundles. There is strong evidence implying that transmembrane channel-like protein (TMC) 1 contributes to the pore-forming subunit of the mature MET channel, yet its expression is delayed (~>P5 in apical outer hair cells, OHCs) compared to the onset of mechanotransduction (~P1). Instead, the temporal expression of TMC2 coincides with this onset, indicating that it could be part of the immature MET channel...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29062271/aminoglycoside-induced-cochleotoxicity-a-review
#14
REVIEW
Meiyan Jiang, Takatoshi Karasawa, Peter S Steyger
Aminoglycoside antibiotics are used as prophylaxis, or urgent treatment, for many life-threatening bacterial infections, including tuberculosis, sepsis, respiratory infections in cystic fibrosis, complex urinary tract infections and endocarditis. Although aminoglycosides are clinically-essential antibiotics, the mechanisms underlying their selective toxicity to the kidney and inner ear continue to be unraveled despite more than 70 years of investigation. The following mechanisms each contribute to aminoglycoside-induced toxicity after systemic administration: (1) drug trafficking across endothelial and epithelial barrier layers; (2) sensory cell uptake of these drugs; and (3) disruption of intracellular physiological pathways...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29049311/a-kinase-inhibitor-library-screen-identifies-novel-enzymes-involved-in-ototoxic-damage-to-the-murine-organ-of-corti
#15
Matthew Ryals, Kwang Pak, Rahul Jalota, Arwa Kurabi, Allen F Ryan
Ototoxicity is a significant side effect of a number of drugs, including the aminoglycoside antibiotics and platinum-based chemotherapeutic agents that are used to treat life-threatening illnesses. Although much progress has been made, the mechanisms that lead to ototoxic loss of inner ear sensory hair cells (HCs) remains incompletely understood. Given the critical role of protein phosphorylation in intracellular processes, including both damage and survival signaling, we screened a library of kinase inhibitors targeting members of all the major families in the kinome...
2017: PloS One
https://www.readbyqxmd.com/read/29033791/protein-synthesis-inhibition-and-activation-of-the-c-jun-n-terminal-kinase-are-potential-contributors-to-cisplatin-ototoxicity
#16
Brian D Nicholas, Shimon Francis, Elizabeth L Wagner, Sibo Zhang, Jung-Bum Shin
Cisplatin has been regarded as an effective and versatile chemotherapeutic agent for nearly 40 years. Though the associated dose-dependent ototoxicity is known, the cellular mechanisms by which cochleovestibular hair cell death occur are not well understood. We have previously shown that aminoglycoside ototoxicity is mediated in part by cytosolic protein synthesis inhibition. Despite a lack of molecular similarity, aminoglycosides were shown to elicit similar stress pathways to cisplatin. We therefore reasoned that there may be some role of protein synthesis inhibition in cisplatin ototoxicity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28949262/monitoring-neonates-for-ototoxicity
#17
Angela C Garinis, Alison Kemph, Anne Marie Tharpe, Joern-Hendrik Weitkamp, Cynthia McEvoy, Peter S Steyger
OBJECTIVES: Neonates admitted to the neonatal intensive care unit (NICU) are at greater risk of permanent hearing loss compared to infants in well mother and baby units. Several factors have been associated with this increased prevalence of hearing loss, including congenital infections (e.g. cytomegalovirus or syphilis), ototoxic drugs (such as aminoglycoside or glycopeptide antibiotics), low birth weight, hypoxia and length of stay. The aetiology of this increased prevalence of hearing loss remains poorly understood...
June 22, 2017: International Journal of Audiology
https://www.readbyqxmd.com/read/28881316/development-and-validation-of-a-sensitive-lc-ms-ms-method-without-derivatization-ion-pairing-agents-for-etimicin-quantification-in-rat-plasma-internal-ear-and-kidney
#18
Lan Yao, Fang Zhou, Mingmin Cai, Ying Peng, Jianguo Sun, Qianying Chen, Xiaoliang Jin, Guangji Wang, Jingwei Zhang
Etimicin (ETM), which belongs to the newest generation of aminoglycosides (AGs), has been proven to not only maintain but also strengthen the advantages of former AGs with relatively less toxicity. Now, it is widely applied for the treatment of bacterial infections in the clinic. Nevertheless, nephrotoxicity and ototoxicity are unavoidable issues for AGs, and while ETM is no exception, the seriousness of these issues is different. To explore the reason why ETM exhibits less toxicity and to better direct the optimization and development of new AGs, it is of great necessity and importance to monitor the pharmacokinetic behaviors of ETM in its potential toxicity target organs, the kidney and internal ear, as well as in plasma...
August 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28878625/non-autonomous-cellular-responses-to-ototoxic-drug-induced-stress-and-death
#19
REVIEW
Shimon P Francis, Lisa L Cunningham
The first major recognition of drug-induced hearing loss can be traced back more than seven decades to the development of streptomycin as an antimicrobial agent. Since then at least 130 therapeutic drugs have been recognized as having ototoxic side-effects. Two important classes of ototoxic drugs are the aminoglycoside antibiotics and the platinum-based antineoplastic agents. These drugs save the lives of millions of people worldwide, but they also cause irreparable hearing loss. In the inner ear, sensory hair cells (HCs) and spiral ganglion neurons (SGNs) are important cellular targets of these drugs, and most mechanistic studies have focused on the cell-autonomous responses of these cell types in response to ototoxic stress...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28814279/musashi-1-is-the-candidate-of-the-regulator-of-hair-cell-progenitors-during-inner-ear-regeneration
#20
Takahiro Wakasaki, Hiroaki Niiro, Siamak Jabbarzadeh-Tabrizi, Mitsuru Ohashi, Takashi Kimitsuki, Takashi Nakagawa, Shizuo Komune, Koichi Akashi
BACKGROUND: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells...
August 16, 2017: BMC Neuroscience
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