scholarly journals The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 201
Author(s):  
Rosa Vona ◽  
Lucia Pallotta ◽  
Martina Cappelletti ◽  
Carola Severi ◽  
Paola Matarrese
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Therapeutic Strategies ◽  
Gastrointestinal Disorders ◽  
Antioxidant Systems ◽  
New Techniques ◽  
Human Pathology ◽  
Substantial Progress ◽  
The Impact

Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies

scholarly journals The Impact of Medium Chain and Polyunsaturated ω-3-Fatty Acids on Amyloid-β Deposition, Oxidative Stress and Metabolic Dysfunction Associated with Alzheimer´s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1991
Author(s):  
Janine Mett
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Energy Metabolism ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Membrane Integrity ◽  
Amyloid Β ◽  
The Elderly ◽  
Medium Chain ◽  
The Impact

Alzheimer’s disease (AD), the most common cause of dementia in the elderly population, is closely linked to a dysregulated cerebral lipid homeostasis and particular changes in brain fatty acid (FA) composition. The abnormal extracellular accumulation and deposition of the peptide amyloid-β (Aβ) is considered as an early toxic event in AD pathogenesis, which initiates a series of events leading to neuronal dysfunction and death. These include the induction of neuroinflammation and oxidative stress, the disruption of calcium homeostasis and membrane integrity, an impairment of cerebral energy metabolism, as well as synaptic and mitochondrial dysfunction. Dietary medium chain fatty acids (MCFAs) and polyunsaturated ω-3-fatty acids (ω-3-PUFAs) seem to be valuable for disease modification. Both classes of FAs have neuronal health-promoting and cognition-enhancing properties and might be of benefit for patients suffering from mild cognitive impairment (MCI) and AD. This review summarizes the current knowledge about the molecular mechanisms by which MCFAs and ω-3-PUFAs reduce the cerebral Aβ deposition, improve brain energy metabolism, and lessen oxidative stress levels.

scholarly journals Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Zi-Huan Zhang ◽  
Jia-Qiang Liu ◽  
Cheng-Di Hu ◽  
Xin-Tong Zhao ◽  
Fei-Yun Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Neuronal Degeneration ◽  
Antioxidant Systems ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Beneficial Effects ◽  
Nrf2 Activation

Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.

Aberrant protein glycosylation in cancer: implications in targeted therapy

2021 ◽  
Author(s):  
Joana G. Rodrigues ◽  
Henrique O. Duarte ◽  
Celso A. Reis ◽  
Joana Gomes
Keyword(s):  
Targeted Therapy ◽  
Tumour Cell ◽  
Rational Design ◽  
Molecular Mechanisms ◽  
Clinical Performance ◽  
Therapeutic Strategies ◽  
Protein Glycosylation ◽  
Immune Checkpoints ◽  
Immunosuppressive Microenvironment ◽  
The Impact

Aberrant cell surface glycosylation signatures are currently known to actively drive the neoplastic transformation of healthy cells. By disrupting the homeostatic functions of their protein carriers, cancer-associated glycans mechanistically underpin several molecular hallmarks of human malignancy. Furthermore, such aberrant glycan structures play key roles in the acquisition of molecular resistance to targeted therapeutic agents, which compromises their clinical efficacy, by modulating tumour cell aggressiveness and supporting the establishment of an immunosuppressive microenvironment. Recent advances in the study of the tumour cell glycoproteome have unravelled previously elusive molecular mechanisms of therapeutic resistance, guided the rational design of novel personalized therapeutic strategies, and may further improve the clinical performance of currently approved anti-cancer targeted agents. In this review, we highlight the impact of glycosylation in cancer targeted therapy, with particular focus on receptor tyrosine kinase-targeted therapy, immune checkpoints blockade therapy, and current developments on therapeutic strategies directed to glycan-binding proteins and other innovative glycan therapeutic strategies.

Mycotoxin Deactivator Improves Performance, Antioxidant Status, and Reduces Oxidative Stress in Nursery Pigs Fed Diets Containing Mycotoxins

2021 ◽  
Author(s):  
Erika Vivian Santos ◽  
Dalton Oliveira Fontes ◽  
Mara da Silveira Benfato ◽  
Fernanda Schäfer Hackenharr ◽  
Tiago Salomon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Control Diet ◽  
Negative Control ◽  
Antioxidant Systems ◽  
Contamination Level ◽  
Standard Diet ◽  
Nursery Pigs ◽  
Inclusion Rate ◽  
The Impact

Abstract Ingestion of mycotoxins can result in many problems, including decreased growth rates and immune suppression. The present study aimed to evaluate the impact of the supplementation of a mycotoxin deactivator composed by adsorbent clay minerals, inactivated fermentation extracts of Saccharomyces cerevisiae, blend of antioxidants, organic acids and botanicals in diets containing added mycotoxins for nursery pigs on their performance and antioxidant status. Ninety pigs weaned with 24 days of age (7.12 ± 0.68 kg of BW) were used. Pigs were housed in pens of 3 animals each according to body weight, litter origin and sex. The dietary treatments consisted of feeding the pigs with: a standard control diet as negative control (NC; mycotoxin levels at accepted regulatory Brazilian Ministry of Agriculture standards Deoxynivalenol (DON): <100 ug/ kg; Zearalenone (ZEA): <20 ug/ kg Fumonisins (FB): <1 mg/ kg); the standard diet added with mycotoxins to reach a low contamination level considered as positive low (PCL-; DON: 900 ug/ kg; ZEA: 100 ug/ kg; FB: 5,000 ug/ kg) without deactivator; a positive low added the deactivator at an inclusion rate of 1 kg/ ton (PCL+); the standard diet added with mycotoxins to reach a high contamination level considered as positive high (PCH-; DON: 4,500 ug/ kg; ZEA: 500 ug/ kg; FB: 18,000 ug/ kg) without the deactivator; and a positive high added the deactivator at an inclusion rate of 5 kg/ ton (PCH+). Pigs were individually weighed at the beginning and at the end of each phase and feed intake recorded based on daily pen intake during the experiment. On d 7, 19, 34 and 43 post-weaning blood samples were drawn for antioxidant analyses. Antioxidant enzymes (glutathione peroxidase (GPx) and total superoxide dismutase (TSOD)), vitamins (Vit A, E, and C), and malondialdehyde (MDA)) were evaluated in erythrocyte and plasma samples. Pigs challenged with mycotoxins presented lower performance traits, decrease in the efficiency of central antioxidant systems (↓GPx, ↓TSOD, ↓Vit A, ↓Vit E and ↓Vit C) and a higher oxidative damage to lipids (↑MDA) when compared to the control and deactivator associated treatments. Our findings showed that the use of a mycotoxin deactivator can mitigate the negative impacts on performance and oxidative stress when animals are subjected to diets contaminated by different levels of mycotoxins.

Abstract 263: Differential Effects of 17ß-Estradiol and 16a-Hydroxyestrone in Oxidative Stress and Proliferative Responses in Human Pulmonary Artery Smooth Muscle Cells - Implications in Pulmonary Arterial Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Katie Y Hood ◽  
Augusto C Montezano ◽  
Margaret R MacLean ◽  
Rhian M Touyz
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Arterial Hypertension ◽  
Cell Growth ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Antioxidant Systems ◽  
Ros Generation ◽  
Ros Production ◽  
Differential Effects ◽  
Pulmonary Arterial

Women develop pulmonary arterial hypertension (PAH) more frequently than men. This may relate, in part, to metabolism of 17β-estradiol (E2), leading to formation of the deleterious metabolite, 16α-hydroxyestrone (16α OHE1), which plays a role in the remodelling of pulmonary arteries. Molecular mechanisms whereby 16αOHE1 influences PASMC remodelling are unclear but ROS may be important, since oxidative stress has been implicated in the pathogenesis of PAH. We hypothesised that E2 and 16αOHE1 leads to Nox-induced ROS production, which promotes PASMC damage. Cultured PASMCs were stimulated with either E2 (1nM) or 16αOHE1 (1nM) in the presence/absence of EHT1864 (100μM, Rac1 inhibitor) or tempol (antioxidant; 10μM). ROS production was assessed by chemiluminescence (O2-) and Amplex Red (H2O2). Antioxidants (thioredoxin, peroxiredoxin 1 and NQ01), regulators of Nrf2 (BACH1, Nrf2) and, marker of cell growth (PCNA) were determined by immunoblotting. E2 increased O2- production at 4h (219 ± 30% vs vehicle; p<0.05), an effect blocked by EHT1864 and tempol. E2 also increased H2O2 generation (152 ± 4%; p<0.05). Thioredoxin, NQ01 and peroxiredoxin1 (71 ± 6%; 78 ± 9%; 69 ± 8%; p<0.05 respectively) levels were decreased by E2 as was PCNA expression (72 ± 2%; p<0.05). 16αOHE1 exhibited a rapid (5 min) and exaggerated increase in ROS production (355 ± 41%; p<0.05), blocked by tempol and EHT1864. This was associated with an increase in Nox4 expression (139 ± 11% vs vehicle, p<0.05). 16αOHE1 increased BACH1, (129 ± 3%; p<0.05), a competitor of Nrf2, which was decreased (92 ± 2%). In contrast, thioredoxin expression was increased by 16aOHE1 (154 ± 22%; p<0.05). PCNA (150 ± 5%) expression was also increased after exposure to 16αOHE1. In conclusion, E2 and 16αOHE1 have differential effects on redox processes associated with PASMC growth. Whereas E2 stimulates ROS production in a slow and sustained manner without effect on cell growth, 16αOHE1 upregulates Nox4 with associated rapid increase in ROS generation and downregulation of antioxidant systems, affecting proliferation. Our findings suggest that E2 -derived metabolites may promote a pro-proliferative PASMC phenotype through Nox4-derived ROS generation. These deleterious effects may impact on vascular remodeling in PAH.

scholarly journals Emerging Roles of Redox-Mediated Angiogenesis and Oxidative Stress in Dermatoses

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Dehai Xian ◽  
Jing Song ◽  
Lingyu Yang ◽  
Xia Xiong ◽  
Rui Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Molecular Mechanisms ◽  
Capillary Tube ◽  
Proteolytic Enzymes ◽  
Skin Tumor ◽  
Antioxidant Systems ◽  
Antiangiogenic Factors ◽  
And Oxidative Stress

Angiogenesis is the process of new vessel formation, which sprouts from preexisting vessels. This process is highly complex and primarily involves several key steps, including stimulation of endothelial cells by growth factors, degradation of the extracellular matrix by proteolytic enzymes, migration and proliferation of endothelial cells, and capillary tube formation. Currently, it is considered that multiple cytokines play a vital role in this process, which consist of proangiogenic factors (e.g., vascular endothelial growth factor, fibroblast growth factors, and angiopoietins) and antiangiogenic factors (e.g., endostatin, thrombospondin, and angiostatin). Angiogenesis is essential for most physiological events, such as body growth and development, tissue repair, and wound healing. However, uncontrolled neovascularization may contribute to angiogenic disorders. In physiological conditions, the above promoters and inhibitors function in a coordinated way to induce and sustain angiogenesis within a limited period of time. Conversely, the imbalance between proangiogenic and antiangiogenic factors could cause pathological angiogenesis and trigger several diseases. With insights into the molecular mechanisms of angiogenesis, increasing reports have shown that a close relationship exists between angiogenesis and oxidative stress (OS) in both physiological and pathological conditions. OS, an imbalance between prooxidant and antioxidant systems, is a cause and consequence of many vascular complains and serves as one of the biomarkers for these diseases. Furthermore, emerging evidence supports that OS and angiogenesis play vital roles in many dermatoses, such as psoriasis, atopic dermatitis, and skin tumor. This review summarizes recent findings on the role of OS as a trigger of angiogenesis in skin disorders, highlights newly identified mechanisms, and introduces the antiangiogenic and antioxidant therapeutic strategies.

scholarly journals Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 985 ◽  
Author(s):  
Abdelhafid Nani ◽  
Babar Murtaza ◽  
Amira Sayed Khan ◽  
Naim Akhtar Khan ◽  
Aziz Hichami
Keyword(s):  
Oxidative Stress ◽  
Mediterranean Diet ◽  
Molecular Mechanisms ◽  
Nutrition Transition ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Metabolic Inflammation ◽  
Dietary Polyphenols ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
The Impact

Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.

scholarly journals Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-24 ◽  
Author(s):  
Mika Reinisalo ◽  
Anna Kårlund ◽  
Ali Koskela ◽  
Kai Kaarniranta ◽  
Reijo O. Karjalainen
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Age Related ◽  
Cellular Defence ◽  
The Impact ◽  
Stilbene Compounds

Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer’s disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed.

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.

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