Oxidative Stress and Inflammation Caused by Cisplatin Ototoxicity

Hearing loss is a significant health problem that can result from a variety of exogenous insults that generate oxidative stress and inflammation. This can produce cellular damage and impairment of hearing. Radiation damage, ageing, damage produced by cochlear implantation, acoustic trauma and ototoxic drug exposure can all generate reactive oxygen species in the inner ear with loss of sensory cells and hearing loss. Cisplatin ototoxicity is one of the major causes of hearing loss in children and adults. This review will address cisplatin ototoxicity. It includes discussion of the mechanisms associated with cisplatin-induced hearing loss including uptake pathways for cisplatin entry, oxidative stress due to overpowering antioxidant defense mechanisms, and the recently described toxic pathways that are activated by cisplatin, including necroptosis and ferroptosis. The cochlea contains G-protein coupled receptors that can be activated to provide protection. These include adenosine A1 receptors, cannabinoid 2 receptors (CB2) and the Sphingosine 1-Phosphate Receptor 2 (S1PR2). A variety of heat shock proteins (HSPs) can be up-regulated in the cochlea. The use of exosomes offers a novel method of delivery of HSPs to provide protection. A reversible MET channel blocker that can be administered orally may block cisplatin uptake into the cochlear cells. Several protective agents in preclinical studies have been shown to not interfere with cisplatin efficacy. Statins have shown efficacy in reducing cisplatin ototoxicity without compromising patient response to treatment. Additional clinical trials could provide exciting findings in the prevention of cisplatin ototoxicity.

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MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation

Current Drug Targets ◽

10.2174/1389450121666200615145552 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1216-1224

Author(s):

Fatemeh Forouzanfar ◽

Samira Asgharzade

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Hair Cell ◽

Noise Exposure ◽

Cell Damage ◽

Sensory Cells ◽

Noise Induced Hearing Loss ◽

Irreversible Damage ◽

Open Access Journals

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

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miRNA and mRNA Profiling Links Connexin Deficiency to Deafness via Early Oxidative Damage in the Mouse Stria Vascularis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.616878 ◽

2021 ◽

Vol 8 ◽

Author(s):

Giulia Gentile ◽

Fabiola Paciello ◽

Veronica Zorzi ◽

Antonio Gianmaria Spampinato ◽

Maria Guarnaccia ◽

...

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Mouse Model ◽

Defense Mechanisms ◽

Expression Profiles ◽

Stria Vascularis ◽

Integrated Analysis ◽

Metabolic Dysregulation ◽

Age Related ◽

Post Transcriptional Regulation

Pathogenic mutations in the non-syndromic hearing loss and deafness 1 (DFNB1) locus are the primary cause of monogenic inheritance for prelingual hearing loss. To unravel molecular pathways involved in etiopathology and look for early degeneration biomarkers, we used a system biology approach to analyze Cx30−/− mice at an early cochlear post-natal developmental stage. These mice are a DFNB1 mouse model with severely reduced expression levels of two connexins in the inner ear, Cx30, and Cx26. Integrated analysis of miRNA and mRNA expression profiles in the cochleae of Cx30−/− mice at post-natal day 5 revealed the overexpression of five miRNAs (miR-34c, miR-29b, miR-29c, miR-141, and miR-181a) linked to apoptosis, oxidative stress, and cochlear degeneration, which have Sirt1 as a common target of transcriptional and/or post-transcriptional regulation. In young adult Cx30−/− mice (3 months of age), these alterations culminated with blood barrier disruption in the Stria vascularis (SV), which is known to have the highest aerobic metabolic rate of all cochlear structures and whose microvascular alterations contribute to age-related degeneration and progressive decline of auditory function. Our experimental validation of selected targets links hearing acquisition failure in Cx30−/− mice, early oxidative stress, and metabolic dysregulation to the activation of the Sirt1–p53 axis. This is the first integrated analysis of miRNA and mRNA in the cochlea of the Cx30−/− mouse model, providing evidence that connexin downregulation determines a miRNA-mediated response which leads to chronic exhaustion of cochlear antioxidant defense mechanisms and consequent SV dysfunction. Our analyses support the notion that connexin dysfunction intervenes early on during development, causing vascular damage later on in life. This study identifies also early miRNA-mediated biomarkers of hearing impairment, either inherited or age related.

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Regeneration of sensory hair cells after acoustic trauma

Science ◽

10.1126/science.3381100 ◽

1988 ◽

Vol 240 (4860) ◽

pp. 1772-1774 ◽

Cited By ~ 530

Author(s):

JT Corwin ◽

DA Cotanche

Keyword(s):

Hearing Loss ◽

Hair Cells ◽

Acoustic Trauma ◽

Sensory Cells ◽

Lesion Site ◽

Supporting Cells ◽

Profound Hearing Loss ◽

Cochlear Hair Cells ◽

Sensory Hair ◽

Sensory Hair Cells

Any loss of cochlear hair cells has been presumed to result in a permanent hearing deficit because the production of these cells normally ceases before birth. However, after acoustic trauma, injured sensory cells in the mature cochlea of the chicken are replaced. New cells appear to be produced by mitosis of supporting cells that survive at the lesion site and do not divide in the absence of trauma. This trauma-induced division of normally postmitotic cells may lead to recovery from profound hearing loss.

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Fluorocitrate Neural Dystrophy of the Guinea Pig Cochlea

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115468 ◽

1975 ◽

Vol 33 ◽

pp. 368-369

Author(s):

G.J. Spector ◽

C.D. Carr ◽

I. Kaufman Arenberg ◽

R.H. Maisel

Keyword(s):

Hearing Loss ◽

Hair Cells ◽

Sodium Phosphate ◽

Sensory Cells ◽

Barium Salt ◽

Perfusion Medium ◽

Cochlear Hair Cells ◽

Neural Degeneration ◽

Sodium Phosphate Buffer ◽

Cochlear Neurons

All studies on primary neural degeneration in the cochlea have evaluated the end stages of degeneration or the indiscriminate destruction of both sensory cells and cochlear neurons. We have developed a model which selectively simulates the dystrophic changes denoting cochlear neural degeneration while sparing the cochlear hair cells. Such a model can be used to define more precisely the mechanism of presbycusis or the hearing loss in aging man.Twenty-two pigmented guinea pigs (200-250 gm) were perfused by the perilymphatic route as live preparations using fluorocitrate in various concentrations (15-250 ug/cc) and at different incubation times (5-150 minutes). The barium salt of DL fluorocitrate, (C6H4O7F)2Ba3, was reacted with 1.0N sulfuric acid to precipitate the barium as a sulfate. The perfusion medium was prepared, just prior to use, as follows: sodium phosphate buffer 0.2M, pH 7.4 = 9cc; fluorocitrate = 15-200 mg/cc; and sucrose = 0.2M.

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Known Hepatoprotectors Act as Antioxidants and Immune Stimulators in Stressed Mice: Perspectives in Animal Health Care

Current Pharmaceutical Design ◽

10.2174/1381612825666190116151628 ◽

2019 ◽

Vol 24 (40) ◽

pp. 4825-4837 ◽

Cited By ~ 2

Author(s):

Gustavo Alberto de la Riva ◽

Francisco Javier López Mendoza ◽

Guillermin Agüero-Chapin

Keyword(s):

Oxidative Stress ◽

Animal Health ◽

Cellular Damage ◽

Farm Animals ◽

Physiological Status ◽

Stress Markers ◽

Glutathione Peroxidases ◽

Transport Chain ◽

Exogenous Compounds ◽

Relationship Of

Background: Oxygen is involved in a variety of physiological reactions in aerobic organisms, such as those produced in the electron transport chain, hydroxylation, and oxygenation. Reactive oxygen species (ROS) are naturally formed as byproducts from these previously reactions involving the O2 molecule; they are made up of superoxide anion (O2−), hydroxyl radical (HO−), hydrogen peroxide (H2O2), nitric oxide (NO), peroxyl (ROO−), and reactive aldehyde (ROCH). Under certain environmental stress conditions, ROS are accumulated causing cellular damage but also triggering the overexpression of several enzyme classes such as superoxide dismutases (SOD), catalases (CAT) and glutathione peroxidases (GPx), which represent an important intrinsic antioxidant defence line. Liver is a key organ in vertebrates including farm animals and human. The oxidative stress plays an important role in systemic malfunctions including hepatic, renal and immunological, disorders. Methods: This review presents a brief update about the relationship of oxidative stress with hepatic, renal and immunological malfunctions in stressed organisms. Cellular and exogenous hepatoprotective compounds share also the ability to scavenge ROS acting as antioxidants and in many cases as stimulators of immune response in stressed organisms. We present the effect of some hepatoprotectors on the hepatic, renal and immunological function in stressed mice by the jointed evaluation of biological and oxidative stress markers. Conclusion: Hepatoprotective effect of several exogenous compounds is very associated with their antioxidant capacity. This fact is relevant for keeping oxidant/antioxidant balance in the respective organs, but also for maintaining the physiological status of the whole organism.

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Oxidative Stress and Inflammation in Renal and Cardiovascular Complications of Diabetes

Biology ◽

10.3390/biology10010018 ◽

2020 ◽

Vol 10 (1) ◽

pp. 18

Author(s):

Amelia Charlton ◽

Jessica Garzarella ◽

Karin A. M. Jandeleit-Dahm ◽

Jay C. Jha

Keyword(s):

Oxidative Stress ◽

Cardiovascular Disease ◽

Tissue Injury ◽

Cardiovascular Complications ◽

Therapeutic Strategies ◽

Cellular Damage ◽

Antioxidant Defenses ◽

Pathological State ◽

Oxygen Species ◽

Emerging Therapies

Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, including renal and cardiovascular disease. A symbiotic relationship also appears to exist between oxidative stress and inflammation. Several emerging therapies target these crucial pathways, to alleviate the burden of the aforementioned diseases. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) and antioxidant defenses, a pathological state which not only leads to direct cellular damage but also an inflammatory cascade that further perpetuates tissue injury. Emerging therapeutic strategies tackle these pathways in a variety of ways, from increasing antioxidant defenses (antioxidants and Nrf2 activators) to reducing ROS production (NADPH oxidase inhibitors and XO inhibitors) or inhibiting the associated inflammatory pathways (NLRP3 inflammasome inhibitors, lipoxins, GLP-1 receptor agonists, and AT-1 receptor antagonists). This review summarizes the mechanisms by which oxidative stress and inflammation contribute to and perpetuate diabetes associated renal and cardiovascular disease along with the therapeutic strategies which target these pathways to provide reno and cardiovascular protection in the setting of diabetes.

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A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

Pharmaceutics ◽

10.3390/pharmaceutics13071041 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1041

Author(s):

Jacqueline Chester ◽

Edan Johnston ◽

Daniel Walker ◽

Melissa Jones ◽

Corina Mihaela Ionescu ◽

...

Keyword(s):

Hearing Loss ◽

Bile Acid ◽

Hearing Aids ◽

Stria Vascularis ◽

Cellular Damage ◽

Relevant Evidence ◽

Neuronal Signalling ◽

Age Related ◽

Recent Advancement ◽

Age Related Hearing Loss

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

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Telomere Architecture Correlates with Aggressiveness in Multiple Myeloma

Cancers ◽

10.3390/cancers13081969 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1969

Author(s):

Aline Rangel-Pozzo ◽

Pak Yu ◽

Sadhana LaL ◽

Yasmin Asbaghi ◽

Luiza Sisdelli ◽

...

Keyword(s):

Multiple Myeloma ◽

Disease Progression ◽

Genomic Instability ◽

Clinical Decision Making ◽

Three Dimensional ◽

Clinical Decision ◽

Response To Treatment ◽

Average Intensity ◽

Patient Response ◽

Smoldering Multiple Myeloma

The prognosis of multiple myeloma (MM), an incurable B-cell malignancy, has significantly improved through the introduction of novel therapeutic modalities. Myeloma prognosis is essentially determined by cytogenetics, both at diagnosis and at disease progression. However, for a large cohort of patients, cytogenetic analysis is not always available. In addition, myeloma patients with favorable cytogenetics can display an aggressive clinical course. Therefore, it is necessary to develop additional prognostic and predictive markers for this disease to allow for patient risk stratification and personalized clinical decision-making. Genomic instability is a prominent characteristic in MM, and we have previously shown that the three-dimensional (3D) nuclear organization of telomeres is a marker of both genomic instability and genetic heterogeneity in myeloma. In this study, we compared in a longitudinal prospective study blindly the 3D telomeric profiles from bone marrow samples of 214 initially treatment-naïve patients with either monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with a minimum follow-up of 5 years. Here, we report distinctive 3D telomeric profiles correlating with disease aggressiveness and patient response to treatment in MM patients, and also distinctive 3D telomeric profiles for disease progression in smoldering multiple myeloma patients. In particular, lower average intensity (telomere length, below 13,500 arbitrary units) and increased number of telomere aggregates are associated with shorter survival and could be used as a prognostic factor to identify high-risk SMM and MM patients.

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Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4535194 ◽

2017 ◽

Vol 2017 ◽

pp. 1-18 ◽

Cited By ~ 96

Author(s):

Tian Tian ◽

Ziling Wang ◽

Jinhua Zhang

Keyword(s):

Oxidative Stress ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Defense Mechanisms ◽

Gastrointestinal Disease ◽

Mucosal Immune Response ◽

Stress Signaling ◽

Substantial Progress ◽

Inflammatory Bowel ◽

Underlying Mechanisms

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose incidence has risen worldwide in recent years. Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of IBD. This review highlights the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms in the gastrointestinal (GI) tract, the involvement of oxidative stress signaling in the initiation and progression of IBD and its relationships with genetic susceptibility and the mucosal immune response. In addition, potential therapeutic strategies for IBD that target oxidative stress signaling are reviewed and discussed. Though substantial progress has been made in understanding the role of oxidative stress in IBD in humans and experimental animals, the underlying mechanisms are still not well defined. Thus, further studies are needed to validate how oxidative stress signaling is involved in and contributes to the development of IBD.

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