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1.
Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction.
Sethuram, R, Bai, D, Abu-Soud, HM
Reproductive sciences (Thousand Oaks, Calif.). 2022;(1):1-6
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Abstract
COVID-19 (coronavirus disease 2019) is the current world health crisis, producing extensive morbidity and mortality across all age groups. Given the established roles of zinc in combating oxidative damage and viral infections, zinc is being trialed as a treatment modality against COVID-19. Zinc also has confirmed roles in both male and female reproduction. The possible depletion of zinc with the oxidative events of COVID-19 is especially relevant to the fertility of affected couples. This review aims to present the pathophysiology of COVID-19, especially in relation to reproductive function; the role of zinc in the COVID-19 disease process; and how zinc depletion in concert with cytokine storm and reactive oxygen species production could affect reproduction. It also highlights research areas to better the understanding of COVID-19 and its impact on fertility and potential ways to mitigate the impact.
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Tinospora cordifolia (Willd.) Miers: Protection mechanisms and strategies against oxidative stress-related diseases.
Arunachalam, K, Yang, X, San, TT
Journal of ethnopharmacology. 2022;:114540
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tinospora cordifolia (Willd.) Miers (Menispermaceae) is a Mediterranean herb, used in Ayurvedic, Siddha, Unani, and folk medicines. The herb is also used in conventional medicine to treat oxidative stress-related diseases and conditions, including inflammation, pain, diarrhea, asthma, respiratory infections, cancer, diabetes, and gastrointestinal disorders. AIM OF THE REVIEW The taxonomy, botanical classification, geographical distribution, and ethnobotanical uses of T. cordifolia, as well as the phytochemical compounds found in the herb, the toxicology of and pharmacological and clinical studies on the effects of T. cordifolia are all covered in this study. MATERIALS AND METHODS To gather information on T. cordifolia, we used a variety of scientific databases, including Scopus, Google Scholar, PubMed, and Science Direct. The information discussed focuses on biologically active compounds found in T. cordifolia, and common applications and pharmacological activity of the herb, as well as toxicological and clinical studies on its properties. RESULTS The findings of this study reveal a connection between the use of T. cordifolia in conventional medicine and its antioxidant, anti-inflammatory, antihypertensive, antidiabetic, anticancer, immunomodulatory, and other biological effects. The entire plant, stem, leaves, root, and extracts of T. cordifolia have been shown to have a variety of biological activities, including antioxidant, antimicrobial, antiviral, antiparasitic, antidiabetic, anticancer, anti-inflammatory, analgesic and antipyretic, hepatoprotective, and cardioprotective impact. Toxicological testing demonstrated that this plant may have medicinal applications. T. cordifolia contains a variety of biologically active compounds from various chemical classes, including alkaloids, terpenoids, sitosterols, flavonoids, and phenolic acids. Based on the reports researched for this review, we believe that chemicals in T. cordifolia may activate Nrf2, which leads to the overexpression of antioxidant enzymes such as CAT, GPx, GST, and GR, and thereby induces the adaptive response to oxidative stress. T. cordifolia is also able to reduce NF-κB signalling by inhibiting PI3K/Akt, activating AMPK and sirtuins, and downregulating PI3K/Akt. CONCLUSIONS Our findings indicate that the pharmacological properties displayed by T. cordifolia back up its conventional uses. Antimicrobial, antiviral, antioxidant, anticancer, anti-inflammatory, antimutagenic, antidiabetic, nephroprotective, gastroprotective, hepatoprotective, and cardioprotective activities were all demonstrated in T. cordifolia stem extracts. To validate pharmacodynamic targets, further research is needed to evaluate the molecular mechanisms of the known compounds against gastrointestinal diseases, inflammatory processes, and microbial infections, as immunostimulants, and in chemotherapy. The T. cordifolia safety profile was confirmed in a toxicological analysis, which prompted pharmacokinetic assessment testing to confirm its bioavailability.
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Critical aspects of the physiological interactions between lead and magnesium.
Wyparło-Wszelaki, M, Machoń-Grecka, A, Wąsik, M, Dobrakowski, M
Journal of biochemical and molecular toxicology. 2022;(2):e22964
Abstract
Despite technological progress, exposure to lead is an ongoing problem. There are many mechanisms governing the toxic effects of lead on the human body. One such mechanism involves the interaction of this xenobiotic with bivalent metal ions, including magnesium. Literature data suggest that the competition between these elements for binding sites at the molecular and cellular levels, as well as at the systemic level, may represent an important aspect of lead toxicity in the human body. This is especially clear in the context of oxidative stress, immune response, and gene expression modifications. This review aims to summarize current knowledge regarding these issues.
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Does Oxidative Stress Management Help Alleviation of COVID-19 Symptoms in Patients Experiencing Diabetes?
Paul, AK, Hossain, MK, Mahboob, T, Nissapatorn, V, Wilairatana, P, Jahan, R, Jannat, K, Bondhon, TA, Hasan, A, de Lourdes Pereira, M, et al
Nutrients. 2022;(2)
Abstract
Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19) with other comorbidities such as diabetes. Diabetes is the most common cause of diabetic nephropathy, which is attributed to hyperglycemia. COVID-19 produces severe complications in people with diabetes mellitus. This article explains how SARS-CoV-2 causes more significant kidney damage in diabetic patients. Importantly, COVID-19 and diabetes share inflammatory pathways of disease progression. SARS-CoV-2 binding with ACE-2 causes depletion of ACE-2 (angiotensin-converting enzyme 2) from blood vessels, and subsequently, angiotensin-II interacts with angiotensin receptor-1 from vascular membranes that produce NADPH (nicotinamide adenine dinucleotide hydrogen phosphate) oxidase, oxidative stress, and constriction of blood vessels. Since diabetes and COVID-19 can create oxidative stress, we hypothesize that COVID-19 with comorbidities such as diabetes can synergistically increase oxidative stress leading to end-stage renal failure and death. Antioxidants may therefore prevent renal damage-induced death by inhibiting oxidative damage and thus can help protect people from COVID-19 related comorbidities. A few clinical trials indicated how effective the antioxidant therapy is against improving COVID-19 symptoms, based on a limited number of patients who experienced COVID-19. In this review, we tried to understand how effective antioxidants (such as vitamin D and flavonoids) can act as food supplements or therapeutics against COVID-19 with diabetes as comorbidity based on recently available clinical, preclinical, or in silico studies.
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Emerging roles of oxidative stress in brain aging and Alzheimer's disease.
Ionescu-Tucker, A, Cotman, CW
Neurobiology of aging. 2021;:86-95
Abstract
Reactive oxygen species (ROS) are metabolic byproducts that are necessary for physiological function but can be toxic at high levels. Levels of these oxidative stressors increase gradually throughout the lifespan, impairing mitochondrial function and damaging all parts of the body, particularly the central nervous system. Emerging evidence suggests that accumulated oxidative stress may be one of the key mechanisms causing cognitive aging and neurodegenerative diseases such as Alzheimer's disease (AD). Here, we synthesize the current literature on the effect of neuronal oxidative stress on mitochondrial dysfunction, DNA damage and epigenetic changes related to cognitive aging and AD. We further describe how oxidative stress therapeutics such as antioxidants, caloric restriction and physical activity can reduce oxidation and prevent cognitive decline in brain aging and AD. Of the currently available therapeutics, we propose that long term physical activity is the most promising avenue for improving cognitive health by reducing ROS while promoting the low levels required for optimal function.
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Use of Thiols in the Treatment of COVID-19: Current Evidence.
Cazzola, M, Rogliani, P, Salvi, SS, Ora, J, Matera, MG
Lung. 2021;(4):335-343
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Abstract
There 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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Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives.
Alwazeer, D, Liu, FF, Wu, XY, LeBaron, TW
Oxidative medicine and cellular longevity. 2021;:5513868
Abstract
COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.
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A review on interplay between small RNAs and oxidative stress in cancer progression.
Das, A, Ganesan, H, Sriramulu, S, Marotta, F, Kanna, NRR, Banerjee, A, He, F, Duttaroy, AK, Pathak, S
Molecular and cellular biochemistry. 2021;(11):4117-4131
Abstract
Oxidative stress has been known to be the underlying cause in many instances of cancer development. The new aspect of cancer genesis that has caught the attention of many researchers worldwide is its connection to non-coding RNAs (ncRNAs). ncRNAs may not be protein coding, but in light of the more recent discovery of their wide range of functions, the term 'dark matter of the genome' has been rendered inapplicable. There is an extensive mention of colon cancer as an example, where some of these ncRNAs and their manipulations have seen significant progress. As of now, the focus is on discovering a non-invasive, cost-effective method for diagnosis that is easier to monitor and can be conducted before visible symptoms indicate cancer in a patient, by which time it may already be too late. The concept of liquid biopsies has revolutionized recent diagnostic measures. It has been possible to detect circulating parts of the cancer genome or other biomarkers in the patients' bodily fluids, resulting in the effective management of the disease. This has led these ncRNAs to be considered effective therapeutic targets and extrinsic modifications in several tumor types, proven to be effective as therapy. However, there is a vast scope for further understanding and pertinent application of our acquired knowledge and expanding it in enhancing the utilization of ncRNAs for a better prognosis, quicker diagnosis, and improved management of cancer. This review explores the prognosis of cancer and related mutations by scrutinizing small ncRNAs in the disease.
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Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?
Roumeliotis, S, Roumeliotis, A, Gorny, X, Mertens, PR
Current vascular pharmacology. 2021;(1):41-54
Abstract
In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.
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Effects of grape products on inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.
Ghalishourani, SS, Farzollahpour, F, Shirinbakhshmasoleh, M, Kolahdouz, S, Ghaedi, E, Behrouzian, M, Haghighian, HK, Campbell, MS, Asbaghi, O, Moodi, V
Phytotherapy research : PTR. 2021;(9):4898-4912
Abstract
This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to determine the effects of grapes and grape products on inflammation and oxidative stress among adults. PubMed, Scopus, ISI Web of Science, and Cochrane Library databases were searched up to July 2020 to identify RCTs investigating the effects of grape and grape products on inflammatory and oxidative stress markers. Weighted mean differences (WMD) were pooled using a random-effects model. Of the 8,962 identified studies, 24 RCTs (27 arms) were included in the statistical analysis. Grape products significantly reduced serum C-reactive protein (CRP) levels (WMD: -0.35 mg/L; 95% CI: -0.62, -0.09, p = .008), but they had no significant effect on serum tumor necrosis factor-alpha (TNF-α) (WMD = -1.08 pg/ml; 95% CI: -2.29, 0.11, p = .07), interleukin-6 (IL-6) (WMD = 0.13 pg/ml; 95% CI: -0.35, 0.60, p = .60), total antioxidant capacity (TAC) (WMD = 0.15; 95% CI: -0.35, 0.65, p = .54), or malondialdehyde (MDA) (WMD = 0.14; 95% CI: -0.64, 0.92, p = .72). The analysis indicated possible decreasing effects of grapes and grape products on CRP, but they might not be able to change IL-6, TNF-α, TAC, and MDA concentrations. Nonetheless, further studies are warranted before definitive conclusions may be reached.