Effect of Antioxidant Therapy on Oxidative Stress In Vivo 2021

: Oxidative stress (OS) is an imbalance between the formation of reactive oxygen and nitrogen species and antioxidant defenses [...]

Effect of Antioxidant Therapy on Oxidative Stress In Vivo

Over the last few decades, many efforts have been put into fields that explore the potential benefits of antioxidants, especially with regards to aging, cancer, cardiovascular diseases, and neurodegenerative diseases. However, despite the positive results in experimental studies, there is no clear evidence of clinical benefit of antioxidant supplementation. In this Editorial we summarize the results of the studies that contributed to the Special Issue “ Effect of Antioxidant therapy on oxidative stress in vivo” . All studies emphasized the potential usefulness of antioxidant supplementation in different pathological situations, while also highlighting the need for further in vitro and in vivo studies

Potential Benefits of Antioxidant Phytochemicals on Endogenous Antioxidants Defences in Chronic Diseases

EDITORIAL Chronic diseases and cancer are worldwide health problems which result in death and disability for millions of people. Numerous epidemiological studies and meta-analyses have suggested that many natural phytochemicals display health-promoting advantages, including the prevention of the most common chronic diseases and cancer. However there are very important topics that need further deepening. Hence, there is still a need to continue in the field of oxidative stress research in chronic diseases and the correlated therapeutic approach, both with diets rich in phytochemicals and antioxidant supplementation. In this Special Issue “Potential benefits of antioxidant phytochemicals on endogenous antioxidants’ defences in chronic diseases the authors emphasized the role of oxidative stress in the pathophysiology of different chronic diseases and dug deep into the mechanisms underlying the potential benefits produced by phytochemical antioxidants. In addition, there was a general consensus on the fact that further in vivo studies are needed to recommend phytochemical antioxidants as an alternative/adjuvant option in the treatment of chronic diseases

Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)- derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage

Intracellular Polyphenol Wine Metabolites Oppose Oxidative Stress and Upregulate Nrf2/ARE Pathway

Moderate wine consumption has been associated with several benefits to human health due to its high polyphenol content. In this study, we investigated whether polyphenols contained in a particular red wine, rich in polyphenols, can pass the cell membrane and switch the oxidant/antioxidant balance toward an antioxidant pattern of THP-1 cells and human cardiomyocytes through a gene regulatory system. First, we identified which metabolite polyphenols present in red wine extract cross cell membranes and may be responsible for antioxidant effects. The results showed that the wine metabolites in treated cells belonged mainly to stilbenes, flavan-3-ols derivatives, and flavonoids. Other metabolites present in cells were not typical wine metabolites. Then, we found that red wine extract dose-dependently lowered reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBHP) up to 50 +/- 7% in both cell lines (p < 0.01). Furthermore, wine extract increased nuclear Nrf2 of about 35 +/- 5% in both cell lines (p < 0.01) and counteracted its reduction induced by TBHP (p < 0.01). The rise in Nrf2 was paralleled by the increase in hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit gene expression (both mRNA and protein) (p < 0.01). These results could help explain the healthful activity of wine polyphenols within cells

Short training in focused cardiac ultrasound in an Internal Medicine department: what realistic skill targets could be achieved?

The importance of focused cardiac ultrasound (FCU) in Internal Medicine care has been recognized by the American Society of Echocardiography. The aim of this study was to test what realistic skill targets could be achieved in FCU, with a relatively short training (theoretical and practical) of 9 h offered to Internal Medicine certification board attending students, and if the addition of further 9 h of training could significantly improve the level of competence. Kappa statistic was used to calculate the inter-observer agreement (trainees/tutor). The agreement between the trainees (who completed the entire training) and the tutor was, respectively, "substantial" (k = 0.71) for the identification of pericardial effusion, "moderate" (k = 0.56-0.54) for the identification of marked right ventricular and left ventricular enlargement, "substantial" (k = 0.77) for the assessment of global cardiac systolic function by visual inspection and "fair" (k = 0.35) for the assessment of size and respiratory change in the diameter of the inferior cave vein (IVC). 18 h training in FCU provided proficiency in obtaining adequate images from the parasternal window without providing the ability to correctly master the apical and subcostal windows. As concerns the interpretative skills, only pericardial effusion and visual estimation of global systolic function could be correctly identified, while ventricular enlargement and IVC prove to be more difficult to evaluate. This study supports incorporating FCU into Internal Medicine fellowship training programs, and should facilitate the design of other similar training courses

New Insights into the Role of Ferroptosis in Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new formof regulated cell deathmainly characterized by altered ironmetabolism, increased polyunsaturated fatty acid peroxidation by reactive oxygen species, depletion of glutathione and inactivation of glutathione peroxidase 4. Recently, a series of studies have indicated that ferroptosis is involved in the death of cardiac and vascular cells and has a key impact on the mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, and heart failure. In this article, we reviewed the molecular mechanism of ferroptosis and the current understanding of the pathophysiological role of ferroptosis in ischemic heart disease and in some cardiomyopathies. Moreover, the comprehension of the machinery governing ferroptosis in vascular cells and cardiomyocytes may provide new insights into preventive and therapeutic strategies in CVDs

Nuclear factor kappa B in patients with a history of unstable angina: case re-opened

This study aims at assessing NF-kB activity in unstable angina (UA) patients free of symptoms after a 1 year follow-u

Lysophosphatidylcholine and Carotid Intima-Media Thickness in Young Smokers: A Role for Oxidized LDL-Induced Expression of PBMC Lipoprotein-Associated Phospholipase A2?

Although cigarette smoking has been associated with carotid intima-media thickness (CIMT) the mechanisms are yet not completely known. Lysophosphatidylcholine (lysoPC), a main product of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, appears to be a major determinant of the pro-atherogenic properties of oxidized LDL (oxLDL) and to induce proteoglycan synthesis, a main player in intimal thickening. In this study we assessed whether cigarette smoking-induced oxidative stress may influence plasma Lp-PLA2 and lysoPC and Lp-PLA2 expression in peripheral blood mononuclear cells (PBMC), as well as the relationship between lysoPC and CIMT.45 healthy smokers and 45 age and sex-matched subjects participated in this study. Smokers, compared to non-smokers, showed increased plasma concentrations of oxLDL, Lp-PLA2 and lysoPC together with up-regulation of Lp-PLA2 (mRNA and protein) expression in PBMC (P<0.001). Plasma Lp-PLA2 positively correlated with both lysoPC (r=0.639, P<0.001) and PBMC mRNA Lp-PLA2 (r=0.484, P<0.001) in all subjects. Moreover CIMT that was higher in smokers (P<0.001), positively correlated with lysoPC (r=0.55, P<0.001). Then in in vitro study we demonstrated that both oxLDL (at concentrations similar to those found in smoker's serum) and oxidized phospholipids contained in oxLDL, were able to up-regulate mRNA Lp-PLA2 in PBMC. This effect was likely due, at least in part, to the enrichment in oxidized phospholipids found in PBMC after exposure to oxLDL. Our results also showed that in human aortic smooth muscle cells lysoPC, at concentrations similar to those found in smokers, increased the expression of biglycan and versican, two main proteoglycans.In smokers a further effect of raised oxidative stress is the up-regulation of Lp-PLA2 expression in PBMC with subsequent increase of plasma Lp-PLA2 and lysoPC. Moreover the correlation between lysoPC and CIMT together with the finding that lysoPC up-regulates proteoglycan synthesis suggests that lysoPC may be a link between smoking and intimal thickening