scholarly journals Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Paweorn Angsutararux ◽  
Sudjit Luanpitpong ◽  
Surapol Issaragrisil
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Chemotherapy Regimen ◽  
Model Development ◽  
Preventive Treatment ◽  
Chemotherapeutic Agents ◽  
Oxygen Species ◽  
Preventive Strategies ◽  
Wide Range ◽  
Threat To Life

Chemotherapy-induced cardiotoxicity is a serious complication that poses a serious threat to life and limits the clinical use of various chemotherapeutic agents, particularly the anthracyclines. Understanding molecular mechanisms of chemotherapy-induced cardiotoxicity is a key to effective preventive strategies and improved chemotherapy regimen. Although no reliable and effective preventive treatment has become available, numerous evidence demonstrates that chemotherapy-induced cardiotoxicity involves the generation of reactive oxygen species (ROS). This review provides an overview of the roles of oxidative stress in chemotherapy-induced cardiotoxicity using doxorubicin, which is one of the most effective chemotherapeutic agents against a wide range of cancers, as an example. Current understanding in the molecular mechanisms of ROS-mediated cardiotoxicity will be explored and discussed, with emphasis on cardiomyocyte apoptosis leading to cardiomyopathy. The review will conclude with perspectives on model development needed to facilitate further progress and understanding on chemotherapy-induced cardiotoxicity.

scholarly journals Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5252
Author(s):  
Yasuyoshi Miyata ◽  
Yuta Mukae ◽  
Junki Harada ◽  
Tsuyoshi Matsuda ◽  
Kensuke Mitsunari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Reactive Oxygen ◽  
Chemotherapeutic Agents ◽  
Malignant Neoplasms ◽  
Oxygen Species ◽  
Efficient Treatment ◽  
Intracellular Ros

Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.

scholarly journals Adrenomedullin Regulates Cellular Glutathione Content via Modulation of γ-Glutamate-Cysteine Ligase Catalytic Subunit Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1357-1364 ◽  
Author(s):  
Jee-Youn Kim ◽  
Ji-Hye Yim ◽  
Jin-Ho Cho ◽  
Jin-Hwan Kim ◽  
Jeong-Hun Ko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Catalytic Subunit ◽  
Oxygen Species ◽  
Glutamate Cysteine Ligase ◽  
Hypoxic Injury ◽  
Wide Range

Adrenomedullin (AM) participates in a wide range of physiological and pathological processes including vasorelaxation, angiogenesis, cancer promotion, and apoptosis. Recently, it has been reported that AM protects a variety of cells against oxidative stress induced by stressors such as hypoxia, ischemia/reperfusion, and hydrogen peroxide through the phosphatidylinositol 3-kinase (PI3K)-dependent pathway. However, the molecular mechanisms underlying the pathway of cell survival against hypoxic injury are largely unknown. In an effort to investigate the survival mechanism against hypoxic injury, we studied the effects of AM on cellular levels of reactive oxygen species, well-known mediators of cell death after oxidative stress, and the mechanism involved in the regulation of reactive oxygen species levels. Here, we show that AM increases γ-glutamate-cysteine ligase (γ-GCL) activity under both hypoxic and normoxic conditions, resulting in an up-regulation of cellular glutathione levels to more than 2-fold higher than basal expression. In addition, we demonstrate that AM induces concentration-dependent expression of the catalytic subunit of γ-GCL (γ-GCLC) at the mRNA and protein levels through the activation of the γ-GCLC promoter fragment sequence from −597 to −320. However, when treated with the PI3K inhibitors, the effects of AM on γ-GCLC expression were completely abrogated, suggesting that a PI3K pathway linked AM with the transcriptional activation of the γ-GCLC promoter. Taken together, our data suggests that AM participates in the regulation of cellular redox status via glutathione synthesis. These results may explain, in part, the mechanism by which AM protects cells against oxidative stress.

Curcuma longa extract reduces the risk of oxidative stress during intense physical exertion

2020 ◽  
pp. 43-49
Author(s):  
A. A. Khisamova ◽  
O. A. Gizinger
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Literature Review ◽  
Curcuma Longa ◽  
Antioxidant Properties ◽  
Physical Exertion ◽  
The Body ◽  
Irreversible Processes ◽  
Oxygen Species ◽  
Wide Range

Increased physical exertion is a catalyst for oxidative stress and the production of reactive oxygen species, which entails irreversible processes in the body, leading to chronic diseases and disability. This article contains a literature review of studies that prove the effect of the antioxidant properties of Curcuma longa on cells under oxidative stress. To search for data, a wide range of literature and databases was explored: Pubmed, Google.Scholar, and Embase.

scholarly journals The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress

2016 ◽  
Vol 198 (11) ◽  
pp. 1563-1575 ◽  
Author(s):  
Kieran D. Collins ◽  
Tessa M. Andermann ◽  
Jenny Draper ◽  
Lisa Sanders ◽  
Susan M. Williams ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Host Cells ◽  
Oxygen Species ◽  
Content Type ◽  
Signaling Complex ◽  
H Pylori

ABSTRACTCytoplasmic chemoreceptors are widespread among prokaryotes but are far less understood than transmembrane chemoreceptors, despite being implicated in many processes. One such cytoplasmic chemoreceptor isHelicobacter pyloriTlpD, which is required for stomach colonization and drives a chemotaxis response to cellular energy levels. Neither the signals sensed by TlpD nor its molecular mechanisms of action are known. We report here that TlpD functions independently of the other chemoreceptors. When TlpD is the sole chemoreceptor, it is able to localize to the pole and recruits CheW, CheA, and at least two CheV proteins to this location. It loses the normal membrane association that appears to be driven by interactions with other chemoreceptors and with CheW, CheV1, and CheA. These results suggest that TlpD can form an autonomous signaling unit. We further determined that TlpD mediates a repellent chemotaxis response to conditions that promote oxidative stress, including being in the presence of iron, hydrogen peroxide, paraquat, and metronidazole. Last, we found that all testedH. pyloristrains express TlpD, whereas other chemoreceptors were present to various degrees. Our data suggest a model in which TlpD coordinates a signaling complex that responds to oxidative stress and may allowH. pylorito avoid areas of the stomach with high concentrations of reactive oxygen species.IMPORTANCEHelicobacter pylorisenses its environment with proteins called chemoreceptors. Chemoreceptors integrate this sensory information to affect flagellum-based motility in a process called chemotaxis. Chemotaxis is employed during infection and presumably aidsH. pyloriin encountering and colonizing preferred niches. A cytoplasmic chemoreceptor named TlpD is particularly important in this process, and we report here that this chemoreceptor is able to operate independently of other chemoreceptors to organize a chemotaxis signaling complex and mediate a repellent response to oxidative stress conditions.H. pyloriencounters and must cope with oxidative stress during infection due to oxygen and reactive oxygen species produced by host cells. TlpD's repellent response may allow the bacteria to escape niches experiencing inflammation and elevated reactive oxygen species (ROS) production.

scholarly journals Sperm oxidative stress: clinical significance and management

2021 ◽  
pp. 19-27
Author(s):  
S. I. Gamidov ◽  
T. V. Shatylko ◽  
A. Yu. Popova ◽  
N. G. Gasanov ◽  
R. S. Gamidov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reactive Oxygen ◽  
Reproductive Technologies ◽  
Male Reproductive System ◽  
Antioxidant Systems ◽  
Oxygen Species

Oxidative stress is one of the leading causes of sperm dysfunction. Excessive amounts of reactive oxygen species can damage sperm membranes and disrupt their DNA integrity, which affects not only the likelihood of getting pregnant naturally, but also the clinical outcomes of assisted reproductive technologies and the risk of miscarriage. Sperm cells are extremely vulnerable to oxidative stress, given the limited functional reserve of their antioxidant systems and the DNA repair apparatus. Lifestyle factors, most of which are modifiable, often trigger generation of reactive oxygen species.  Both the lifestyle modification and use of antioxidant dietary supplements are adequate and compatible ways to combat male oxidative stress-associated infertility. The search for other internal and external sources of reactive oxygen species, the identification of the etiology of oxidative stress and treatment of respective diseases are necessary for the successful regulation of redox processes in the male reproductive system in clinical practice, which is required not only to overcome infertility, but also to prevent induced epigenetic disorders in subsequent generations. The article presents the analysis of the molecular mechanisms of male idiopathic infertility. The authors provide an overview of how to prevent oxidative stress as one of the causes of subfebrile fever. The article provides an overview of modern therapeutics, as well as the options for eliminating the consequences of the effect of reactive oxygen species on spermatogenesis and male reproductive system in general.

scholarly journals Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mariachiara Buccarelli ◽  
Quintino Giorgio D’Alessandris ◽  
Paola Matarrese ◽  
Cristiana Mollinari ◽  
Michele Signore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Strong Increase ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, characterized by a poor prognosis mainly due to recurrence and therapeutic resistance. It has been widely demonstrated that glioblastoma stem-like cells (GSCs), a subpopulation of tumor cells endowed with stem-like properties is responsible for tumor maintenance and progression. Moreover, it has been demonstrated that GSCs contribute to GBM-associated neovascularization processes, through different mechanisms including the transdifferentiation into GSC-derived endothelial cells (GdECs). Methods In order to identify druggable cancer-related pathways in GBM, we assessed the effect of a selection of 349 compounds on both GSCs and GdECs and we selected elesclomol (STA-4783) as the most effective agent in inducing cell death on both GSC and GdEC lines tested. Results Elesclomol has been already described to be a potent oxidative stress inducer. In depth investigation of the molecular mechanisms underlying GSC and GdEC response to elesclomol, confirmed that this compound induces a strong increase in mitochondrial reactive oxygen species (ROS) in both GSCs and GdECs ultimately leading to a non-apoptotic copper-dependent cell death. Moreover, combined in vitro treatment with elesclomol and the alkylating agent temozolomide (TMZ) enhanced the cytotoxicity compared to TMZ alone. Finally, we used our experimental model of mouse brain xenografts to test the combination of elesclomol and TMZ and confirmed their efficacy in vivo. Conclusions Our results support further evaluation of therapeutics targeting oxidative stress such as elesclomol with the aim of satisfying the high unmet medical need in the management of GBM.

Curcumin-C3 Complexed with α-, β-cyclodextrin Exhibits Antibacterial and Antioxidant Properties Suitable for Cancer Treatments

2020 ◽  
Vol 20 (12) ◽  
pp. 988-1001 ◽  
Author(s):  
Desu N. K. Reddy ◽  
Ramya Kumar ◽  
Shao-Pin Wang ◽  
Fu-Yung Huang
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Diseases ◽  
Curcuma Longa ◽  
Antioxidant Properties ◽  
Preventive Treatment ◽  
Entrapment Efficiency ◽  
Cancer Treatments ◽  
Molar Ratios ◽  
Transmission Electron ◽  
Wide Range

Background: The curcumin-C3 (cur-C3) complex obtained from Curcuma longa rhizome is a combination of three curcuminoids, namely, curcumin, dimethoxycurcumin, and bisdemethoxycurcumin. Cur and curcuminoids have been extensively researched for their wide range of therapeutic properties against inflammatory diseases, diabetes, and cancer. Objective: In spite of their extensive medicinal properties, cur and curcuminoids have poor solubility and bioavailability due to their hydrophobicity. This limitation can be overcome by complexing cur-C3 with natural cyclic oligosaccharides, such as Cyclodextrin (CD). Methods: In this study, cur-C3 and CD (α, β) inclusion complexes (ICs) were prepared with different molar ratios and characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy, X-ray diffraction, and transmission electron microscopy. Results: The cur-C3 cyclodextrin ICs showed an increased entrapment efficiency of 97.8% and improved antioxidant activity compared to cur and can be used as an antioxidant to reduce cancer-related oxidative stress. Additionally, α- CD ICs of curcumin-C3 caused an increase in growth inhibition of Staphylococcus aureus. Conclusion: Our findings suggest that both α- and β-CDs are suitable carriers for cur-C3 and can be used as an effective treatment for cancer-associated oxidative stress and as a preventive treatment for nosocomial infections and pneumonia.

scholarly journals Nitric Oxide, Oxidative Stress, andp66ShcInterplay in Diabetic Endothelial Dysfunction

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Alessandra Magenta ◽  
Simona Greco ◽  
Maurizio C. Capogrossi ◽  
Carlo Gaetano ◽  
Fabio Martelli
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Complex Interplay ◽  
Cell Dysfunction ◽  
Intracellular Ros ◽  
No Bioavailability

Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production,p66Shcprotein.

scholarly journals Oxidative Stress and ROS-Mediated Signaling in Leukemia: Novel Promising Perspectives to Eradicate Chemoresistant Cells in Myeloid Leukemia

2021 ◽  
Vol 22 (5) ◽  
pp. 2470
Author(s):  
Silvia Trombetti ◽  
Elena Cesaro ◽  
Rosa Catapano ◽  
Raffaele Sessa ◽  
Alessandra Lo Bianco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Cellular Redox ◽  
Ros Homeostasis

Myeloid leukemic cells are intrinsically under oxidative stress due to impaired reactive oxygen species (ROS) homeostasis, a common signature of several hematological malignancies. The present review focuses on the molecular mechanisms of aberrant ROS production in myeloid leukemia cells as well as on the redox-dependent signaling pathways involved in the leukemogenic process. Finally, the relevance of new chemotherapy options that specifically exert their pharmacological activity by altering the cellular redox imbalance will be discussed as an effective strategy to eradicate chemoresistant cells.

scholarly journals 4-PHENYLBUTYRATE: MOLECULAR MECHANISMS AND AGING INTERVENTION POTENTIAL

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
Michael R Bene ◽  
Kevin Thyne ◽  
Jonathan Dorigatti ◽  
Adam B Salmon
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Molecular Mechanisms ◽  
Oxidative Stress Response ◽  
Chemical Chaperone ◽  
Mouse Muscle ◽  
Age Related ◽  
Primary Mouse ◽  
Wide Range

Abstract 4-Phenylbutyrate (PBA) is a FDA approved drug for treating patients with urea cycle disorders. Additionally, PBA acts upon several pathways thought of as important modifiers of aging including: histone deacetylation, proteostasis as a chemical chaperone, and stress resistance by regulating expression of oxidative stress response proteins. PBA has also been shown to extend lifespan and improve markers of age-related health in Drosophila. Due to its wide range of effects PBA has been investigated for use in numerous age-related disorders including neurodegenerative and cardiovascular diseases. To better understand the effects of PBA on the molecular level, we used both in cellulo and in vivo studies. Treatment of primary mouse fibroblasts, C2C12 mouse muscle cells, and NCTC 1469 mouse liver cells with PBA demonstrated differential responses among cell lines to upregulation of oxidative stress response and histone acetylation. Specifically, upregulation of the oxidative stress response protein DJ-1 by PBA was found to have a corresponding dose response curve to histone H3 acetylation in primary fibroblasts. To study effects of PBA in vivo, four cohorts of HET3 mice were treated with PBA at different doses in drinking water for 4 weeks. PBA was well tolerated and led to different effects on body composition dependent on the sex of mice. We are currently investigating the molecular effects of PBA treatment in multiple tissues samples from these mice. The potential of PBA to alter many fundamental pathways, and specifically those related to stress responses, make it an attractive prospect for treatment of many age-related disorders.

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