Worse Course and Bad Prognosis of COVID-19 in Hyper-Homocysteinemia: Role of Some B-Group Vitamins and of Other Compounds

Background: Increased homocysteine serum levels (HHcy) induce Endothelium Dysfunction (ED), responsible of the activation of some proinflammatory agents (“cytokine storm”), the imbalance between vasodilation and vasoconstriction with vasoconstrictive prevalence, increased oxidative stress and hyper-coagulability. Methods: All these events can worsen the course of COVID-19 in HHcy- patients, favoring the evolution towards vasculitis, thromboembolic complications, multi-organ dysfunction until acute respiratory distress and failure. Results: Therefore, Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) also called COVID-19, elapses more dangerously in patients affected by HHcy and can easily complicate with thromboembolic events. But, some vitamins of B-group and other substances could positively affect both high Hcy levels and thrombotic complications of SARS-CoV-2 happening in lungs and other districts. Conclusions: COVID-19 can have a dangerous evolution and a bad prognosis in patients with HHcy. Concerning this, some compounds seem to exert beneficial effects on HHcy, inflammatory and coagulopathic complications.

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Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽

10.3390/antiox10020160 ◽

2021 ◽

Vol 10 (2) ◽

pp. 160

Author(s):

Vladana Domazetovic ◽

Irene Falsetti ◽

Caterina Viglianisi ◽

Kristian Vasa ◽

Cinzia Aurilia ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Properties ◽

Intestinal Barrier ◽

Protective Role ◽

Intercellular Adhesion Molecule ◽

Intestinal Epithelial ◽

Intercellular Adhesion Molecule 1 ◽

Beneficial Effects ◽

Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

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Use of Thiols in the Treatment of COVID-19: Current Evidence

Lung ◽

10.1007/s00408-021-00465-3 ◽

2021 ◽

Author(s):

Mario Cazzola ◽

Paola Rogliani ◽

Sundeep Santosh Salvi ◽

Josuel Ora ◽

Maria Gabriella Matera

Keyword(s):

Oxidative Stress ◽

Influenza Virus Infection ◽

Current Evidence ◽

Low Molecular Weight ◽

Oxygen Species ◽

Cytokine Storm ◽

Antioxidant Defences ◽

Antioxidant Molecule ◽

Novel Therapeutic

AbstractThere is a possible role for oxidative stress, a state characterized by an altered balance between the production of free radicals or reactive oxygen species (ROS) and antioxidant defences, in coronavirus disease 2019 (COVID-19), the genesis of which is quite complex. Excessive oxidative stress could be responsible for the alveolar damage, thrombosis, and red blood cell dysregulation observed in COVID-19. Apparently, deficiency of glutathione (GSH), a low-molecular-weight thiol that is the most important non-enzymatic antioxidant molecule and has the potential to keep the cytokine storm in check, is a plausible explanation for the severe manifestations and death in COVID-19 patients. Thiol drugs, which are considered mucolytic, also possess potent antioxidant and anti-inflammatory properties. They exhibit antibacterial activity against a variety of medically important bacteria and may be an effective strategy against influenza virus infection. The importance of oxidative stress during COVID-19 and the various pharmacological characteristics of thiol-based drugs suggest a possible role of thiols in the treatment of COVID-19. Oral and intravenous GSH, as well as GSH precursors such as N-acetylcysteine (NAC), or drugs containing the thiol moiety (erdosteine) may represent a novel therapeutic approach to block NF-kB and address the cytokine storm syndrome and respiratory distress observed in COVID-19 pneumonia patients

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New Perspectives of S-Adenosylmethionine (SAMe) Applications to Attenuate Fatty Acid-Induced Steatosis and Oxidative Stress in Hepatic and Endothelial Cells

Molecules ◽

10.3390/molecules25184237 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4237 ◽

Cited By ~ 1

Author(s):

Laura Vergani ◽

Francesca Baldini ◽

Mohamad Khalil ◽

Adriana Voci ◽

Pietro Putignano ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Fatty Acid ◽

Lipid Accumulation ◽

Endothelium Dysfunction ◽

Beneficial Effects ◽

Mitochondrial Fatty Acid ◽

Oxidant Production ◽

Pleiotropic Functions ◽

And Oxidative Stress

S-adenosylmethionine (SAMe) is an endogenous methyl donor derived from ATP and methionine that has pleiotropic functions. Most SAMe is synthetized and consumed in the liver, where it acts as the main methylating agent and in protection against the free radical toxicity. Previous studies have shown that the administration of SAMe as a supernutrient exerted many beneficial effects in various tissues, mainly in the liver. In the present study, we aimed to clarify the direct effects of SAMe on fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells. Hepatoma FaO cells and endothelial HECV cells exposed to a mixture of oleate/palmitate are reliable models for hepatic steatosis and endothelium dysfunction, respectively. Our findings indicate that SAMe was able to significantly ameliorate lipid accumulation and oxidative stress in hepatic cells, mainly through promoting mitochondrial fatty acid entry for β-oxidation and external triglyceride release. SAMe also reverted both lipid accumulation and oxidant production (i.e., ROS and NO) in endothelial cells. In conclusion, these outcomes suggest promising beneficial applications of SAMe as a nutraceutical for metabolic disorders occurring in fatty liver and endothelium dysfunction.

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Role of Oxidative Stress in Diabetic Retinopathy and the Beneficial Effects of Flavonoids

Current Pharmaceutical Design ◽

10.2174/1381612824666180515151043 ◽

2018 ◽

Vol 24 (19) ◽

pp. 2180-2187 ◽

Cited By ~ 7

Author(s):

Mohammad Shamsul Ola ◽

Dalia Al-Dosari ◽

Abdullah S. Alhomida

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Experimental Studies ◽

Developed Countries ◽

Retinal Damage ◽

Beneficial Effects ◽

Diabetic Retina ◽

Retinal Pathology ◽

Dietary Flavonoids

Diabetic Retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious change through dysregulation of cellular physiology that damages both neuronal and vascular cells. In this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contribute to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by our group and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the beneficial effects of the six major flavonoid families, such as flavanones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flavanoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in diabetes. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR.

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Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21239015 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9015

Author(s):

Daniel Janitschke ◽

Anna A. Lauer ◽

Cornel M. Bachmann ◽

Martin Seyfried ◽

Heike S. Grimm ◽

...

Keyword(s):

Gene Regulation ◽

Transcriptional Regulation ◽

Expression Patterns ◽

Wild Type ◽

Neuronal Function ◽

Purine Base ◽

Unique Role ◽

Beneficial Effects ◽

Other Substances

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.

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Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽

10.3390/antiox9101018 ◽

2020 ◽

Vol 9 (10) ◽

pp. 1018

Author(s):

Caitlyn A. Mullins ◽

Ritchel B. Gannaban ◽

Md Shahjalal Khan ◽

Harsh Shah ◽

Md Abu B. Siddik ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Homeostasis ◽

Dorsal Striatum ◽

Brain Regions ◽

Therapeutic Interventions ◽

Low Grade ◽

Obesity Prevalence ◽

Beneficial Effects ◽

The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

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Modulatory Effects of L-Arginine on Methylxanthine-Induced Cardiotoxicity in Rats: A Differential Role for Nitric Oxide (NO)

Journal of Integrative Cardiology Open Access ◽

10.31487/j.jicoa.2021.03.09 ◽

2021 ◽

pp. 1-6

Author(s):

Arunabha Ray ◽

Md Shamsuzzaman ◽

Jagdish C. Joshi ◽

Kavita Gulati ◽

Arunabha Ray

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Adverse Effect ◽

Troponin I ◽

Therapeutic Index ◽

Airway Disease ◽

Cardiac Biomarkers ◽

Qtc Interval ◽

Beneficial Effects

Methylxanthines are potent bronchodilators used in obstructive airway disease like COPD and bronchial asthma, but the narrow therapeutic index and resultant adverse effect profile have restricted their use. Novel beneficial effects and modes of action are now being proposed for these pharmacoeconomically viable agents. Cardiotoxicity is a prominent adverse effect of methylxanthone and thus we investigated possible mechanisms for such toxicity with an aim to devise ameliorative strategies for counteracting such undesirable effects. In view of the cardioprotective role of nitric oxide (NO) and NO mimetics, the present study investigated the possible modulatory role of L-arginine, a NO precursor, in theophylline induced cardiotoxicity in rats, with a view to exploring strategies for facilitating the safe use of this drug. The methylxanthine, aminophylline induced cardiotoxic effects like increased heart rat, raised mean BP, inverted T-waves and prolonged QTc interval (in ECG). These were accompanied by increased levels of cardiac biomarkers like Troponin-I, CPK-MB, and ADMA. Oxidative stress markers like MDA were elevated whereas, antioxidant defence markers like GSH and SOD were suppressed. Co-administration of L-arginine (with aminophylline) had dose-related effects on cardiac function (heart rate, mean BP, ECG changes) and cardiospecific biomarkers (TnI, CPK-MB, ADMA) - the lower dose being protective whereas the higher dose potentiating some of the cardiac effects and cardiospecific/oxidative stress biomarker levels. The results indicate a biphasic involvement of NO in the cardiotoxic effect of theophylline and suggests possible interactions of NO with reactive oxygen species during such modulations of cardiotoxicity.

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Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5021694 ◽

2020 ◽

Vol 2020 ◽

pp. 1-29

Author(s):

Teresa Cunha-Oliveira ◽

Liliana Montezinho ◽

Catarina Mendes ◽

Omidreza Firuzi ◽

Luciano Saso ◽

...

Keyword(s):

Oxidative Stress ◽

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Therapeutic Benefit ◽

Pharmacological Intervention ◽

Antioxidant Compounds ◽

Pathological Feature ◽

Beneficial Effects ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease or Charcot disease, is a fatal neurodegenerative disease that affects motor neurons (MNs) and leads to death within 2–5 years of diagnosis, without any effective therapy available. Although the pathological mechanisms leading to ALS are still unknown, a wealth of evidence indicates that an excessive reactive oxygen species (ROS) production associated with an inefficient antioxidant defense represents an important pathological feature in ALS. Substantial evidence indicates that oxidative stress (OS) is implicated in the loss of MNs and in mitochondrial dysfunction, contributing decisively to neurodegeneration in ALS. Although the modulation of OS represents a promising approach to protect MNs from degeneration, the fact that several antioxidants with beneficial effects in animal models failed to show any therapeutic benefit in patients raises several questions that should be analyzed. Using specific queries for literature search on PubMed, we review here the role of OS-related mechanisms in ALS, including the involvement of altered mitochondrial function with repercussions in neurodegeneration. We also describe antioxidant compounds that have been mostly tested in preclinical and clinical trials of ALS, also describing their respective mechanisms of action. While the description of OS mechanism in the different mutations identified in ALS has as principal objective to clarify the contribution of OS in ALS, the description of positive and negative outcomes for each antioxidant is aimed at paving the way for novel opportunities for intervention. In conclusion, although antioxidant strategies represent a very promising approach to slow the progression of the disease, it is of utmost need to invest on the characterization of OS profiles representative of each subtype of patient, in order to develop personalized therapies, allowing to understand the characteristics of antioxidants that have beneficial effects on different subtypes of patients.

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The comprehensive mechanistic insight into the effects of vitamin D on dementia – a review

Nutrition & Food Science ◽

10.1108/nfs-08-2021-0256 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Jaber Jafarzadeh ◽

Laleh Payahoo ◽

Mohammad Yousefi ◽

Ali Barzegar

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Bone Mineralization ◽

Serum Levels ◽

Skeletal Maturation ◽

Micronutrient Deficiencies ◽

Neuroprotective Effects ◽

Content Type ◽

Modifiable Factors

Purpose This paper aims to depict the mechanistic role of vitamin D on dementia prevention, relief of the severity and the complication of the disease. All papers indexed in scientific databases, including Scopus, Elsevier, PubMed, Embase and Google Scholar between 2000 and 2021 were extracted and discussed. To present the mechanistic role of vitamin D in declining the severity of dementia, keywords including dementia, vitamin D, oxidative stress, inflammation, amyloid beta-Peptides were used. Design/methodology/approach Dementia is a prevalent cognitive disorder worldwide, especially in elderly people, which is accompanied by serious disabilities. Besides genetic, biological and lifestyle factors are involved in the incidence of dementia. An unhealthy diet along with micronutrient deficiencies are among modifiable factors. Vitamin D is one of the important micronutrients in brain health. Besides the involvement in gene expression, bone mineralization, apoptosis, inflammation, skeletal maturation, neurotropic action and hemostasis of phosphate and calcium, vitamin D also exerts neuroprotective effects via genomic and non-genomic pathways. Findings Vitamin D up-regulates the expression of various genes involved in dementia incidence via various mechanisms. Decreasing oxidative stress and the neuro-inflammatory cytokines levels, regulation of the expression of alternated Proteins including Tau and Amyloid-ß, calcium homeostasis in the central nervous system and also vascular are considered main mechanisms. Originality/value Considering the importance of diet in preventing dementia, adherence to a healthy diet that provides essential nutrients to brain function seems to be urgent. Controlling serum levels of vitamin D periodically and providing vitamin D by related sources or supplements, if there is a deficiency, is recommended. Future studies are needed to clarify other related mechanisms.

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Sirt1 Inhibits Oxidative Stress in Vascular Endothelial Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7543973 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 51

Author(s):

Weijin Zhang ◽

Qiaobing Huang ◽

Zhenhua Zeng ◽

Jie Wu ◽

Yaoyuan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Protective Role ◽

Vascular Endothelial ◽

Protective Effects ◽

Beneficial Effects ◽

Key Factor ◽

Antioxidative Stress

The vascular endothelium is a layer of cells lining the inner surface of vessels, serving as a barrier that mediates microenvironment homeostasis. Deterioration of either the structure or function of endothelial cells (ECs) results in a variety of cardiovascular diseases. Previous studies have shown that reactive oxygen species (ROS) is a key factor that contributes to the impairment of ECs and the subsequent endothelial dysfunction. The longevity regulator Sirt1 is a NAD+-dependent deacetylase that has a potential antioxidative stress activity in vascular ECs. The mechanisms underlying the protective effects involve Sirt1/FOXOs, Sirt1/NF-κB, Sirt1/NOX, Sirt1/SOD, and Sirt1/eNOs pathways. In this review, we summarize the most recent reports in this field to recapitulate the potent mechanisms involving the protective role of Sirt1 in oxidative stress and to highlight the beneficial effects of Sirt1 on cardiovascular functions.

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