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Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19.
De Flora, S, Balansky, R, La Maestra, S
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020;(10):13185-13193
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Abstract
COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID-19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin-converting enzyme 2 thereby hampering penetration of SARS-CoV-2 into cells. Based on a broad range of antioxidant and anti-inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID-19, as it was previously demonstrated for influenza and influenza-like illnesses. Moreover, high-dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID-19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.
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Research progress on the biological activities of selenium polysaccharides.
Zhou, N, Long, H, Wang, C, Yu, L, Zhao, M, Liu, X
Food & function. 2020;(6):4834-4852
Abstract
Selenium polysaccharides are a new type of functional polysaccharide that combines inorganic selenium with polysaccharides to form an organic selenium product. Selenium polysaccharides are obtained using three different methods, have no toxicity or side effects, and are easily absorbed and utilized by the body. A number of studies have demonstrated that selenium polysaccharides possess better antioxidant, antitumour, immune regulation, hypoglycaemic, and heavy metal removal activities than that of either polysaccharides or inorganic selenium. Selenium polysaccharides have gradually become a research topic of interest for the development of functional foods and pharmaceutical products. However, further studies are required to investigate the structures and mechanisms of selenium polysaccharides. At present, reviews that focus on the bioactivities of selenium polysaccharides are lacking. The aim of this study was to summarize the selenium polysaccharide bioactivity reports from the past decades, describe the mechanisms and shortcomings of these studies, and evaluate the need for further development.
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Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors.
Biswas, P, Dellanoce, C, Vezzoli, A, Mrakic-Sposta, S, Malnati, M, Beretta, A, Accinni, R
Nutrients. 2020;(11)
Abstract
The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.
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Hydrogen sulfide regulates the activity of antioxidant enzymes through persulfidation and improves the resistance of tomato seedling to Copper Oxide nanoparticles (CuO NPs)-induced oxidative stress.
Li, J, Shi, C, Wang, X, Liu, C, Ding, X, Ma, P, Wang, X, Jia, H
Plant physiology and biochemistry : PPB. 2020;:257-266
Abstract
Hydrogen sulfide (H2S), a small gaseous signaling molecule, regulates antioxidase activity and improves plant tolerance to oxidative stress. The phytotoxic effect of Copper Oxide (II) nanoparticles (CuO NPs) is due to oxidative stress. Here, we show that H2S-mediated persulfidation of antioxidase is essential for an effective stress response of tomato exposed to CuO NPs. The CuO NP-induced increase in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels was significantly reduced by treatment with the H2S donor NaHS. In vivo, NaHS increased superoxide dismutase (SOD), ascorbate peroxidase (APX) and peroxidase (POD) activities under CuO NP stress. In vitro, NaHS increased APX and POD activities but decreased catalase (CAT) activity. Persulfidation existed in recombinant SlCAT1, SlcAPX1 and SlPOD5 proteins. The persulfidatied cysteine (Cys) residues were verified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), revealing their position on the protein surface. Cys234 of SlCAT1 is located in the immune-responsive domain and close to the enzyme activity domain. Cys234 of SlcAPX1 and Cys 61 SlPOD5 are located in the enzyme activity domain. Persulfidation increased SlcAPX1 and SlPOD5 activities but decreased SlCAT1 activity. These data indicate that H2S-mediated persulfidation posttranslationally regulates the activities of CAT, APX and POD, thereby enhancing the plant's response to oxidative stress. Additionally, this work provides an experimental approach for the study of persulfidation in plants.
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A randomized, double-blind, placebo-controlled clinical trial, evaluating the garlic supplement effects on some serum biomarkers of oxidative stress, and quality of life in women with rheumatoid arthritis.
Moosavian, SP, Paknahad, Z, Habibagahi, Z
International journal of clinical practice. 2020;(7):e13498
Abstract
AIM: Rheumatoid arthritis (RA), is a prevalent immune-inflammatory disease, which is associated with disabling pain. Oxidative stress might play a role in RA pathogenesis and outcomes. According to the antioxidant properties of garlic, the current study was performed to evaluate the garlic supplement effects on some serum levels of oxidative stress biomarkers, and quality of life in patients with rheumatoid arthritis. METHODS Seventy women with RA participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The patients were randomly divided into two groups, receiving two tablets of either 500 mg garlic or placebo daily for 8 weeks. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) and quality of life were determined at baseline and end of week 8. A health assessment questionnaire (HAQ) was used to evaluate the quality of life related to health. RESULTS Of 70 patients enrolled in the trial, 62 subjects were included in the final analysis. At the end of the study, there was a significant increase in serum levels of TAC in the garlic group as compared with the placebo group (26.58 ± 77.30 nmol of Trolox equivalent/ml vs 16.11 ± 0.92 nmol of Trolox equivalent/mL; P = .026). In addition, MDA levels were significantly decreased in the intervention group compared with the control group (-0.82 ± 1.99 nmol/mL vs 0.36 ± 2.57 nmol/mL; P = .032). Pain after activity and HAQ scores decreased in the garlic group compared with the placebo (-11.96 ± 13.43 mm vs -0.06 ± 13.41 mm; P < .001, 0.17 ± 20 vs 0.05 ± 0.15; P < .001, respectively). CONCLUSIONS The findings suggest that garlic supplementation for 8 weeks resulted in significant improvements in oxidative stress, HAQ in women with RA.
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Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression.
Schönrich, G, Raftery, MJ, Samstag, Y
Advances in biological regulation. 2020;:100741
Abstract
Pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses an unprecedented challenge to healthcare systems due to the lack of a vaccine and specific treatment options. Accordingly, there is an urgent need to understand precisely the pathogenic mechanisms underlying this multifaceted disease. There is increasing evidence that the immune system reacts insufficiently to SARS-CoV-2 and thus contributes to organ damage and to lethality. In this review, we suggest that the overwhelming production of reactive oxygen species (ROS) resulting in oxidative stress is a major cause of local or systemic tissue damage that leads to severe COVID-19. It increases the formation of neutrophil extracellular traps (NETs) and suppresses the adaptive arm of the immune system, i.e. T cells that are necessary to kill virus-infected cells. This creates a vicious cycle that prevents a specific immune response against SARS-CoV-2. The key role of oxidative stress in the pathogenesis of severe COVID-19 implies that therapeutic counterbalancing of ROS by antioxidants such as vitamin C or NAC and/or by antagonizing ROS production by cells of the mononuclear phagocyte system (MPS) and neutrophil granulocytes and/or by blocking of TNF-α can prevent COVID-19 from becoming severe. Controlled clinical trials and preclinical models of COVID-19 are needed to evaluate this hypothesis.
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The Interplay Between Antioxidants and the Immune System: A Promising Field, Still Looking for Answers.
Romiti, GF, Corica, B, Raparelli, V, Basili, S, Cangemi, R
Nutrients. 2020;(6)
Abstract
Modulation of the immune response has long been proposed as a therapeutic target in several widespread diseases, including cancer, autoimmune disorders, cardiovascular diseases[...].
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Dietary interventions for multiple sclerosis-related outcomes.
Parks, NE, Jackson-Tarlton, CS, Vacchi, L, Merdad, R, Johnston, BC
The Cochrane database of systematic reviews. 2020;(5):CD004192
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Abstract
BACKGROUND Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012). OBJECTIVES To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS. SEARCH METHODS On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data. SELECTION CRITERIA We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5. MAIN RESULTS We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by established criteria, presenting to MS clinics in Europe, North America, and the Middle East. Study design varied considerably, although all trials had at least one methodological issue leading to unknown or high risk of bias. Trials examined: supplementation to increase polyunsaturated fatty acids (PUFAs) (11 trials); a variety of antioxidant supplements (10 trials); dietary programmes (3 trials); and other dietary supplements (e.g. acetyl L-carnitine, biotin, creatine, palmitoylethanolamide, probiotic, riboflavin) (6 trials). In three trials comparing PUFAs with monounsaturated fatty acids (MUFAs), the evidence was very uncertain concerning difference in relapses (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.20; 3 studies, 217 participants; 75% in the PUFA group versus 74% in the MUFA group; very low-certainty evidence). Among four trials comparing PUFAs with MUFAs, there may be little to no difference in global impression of deterioration (RR 0.85, 95% CI 0.71 to 1.03; 4 studies, 542 participants; 40% in the PUFA group versus 47% in the MUFA group; low-certainty evidence). In two trials comparing PUFAs with MUFAs (102 participants), there was very low-certainty evidence for change in disability progression. None of the PUFA versus MUFA trials examined MRI outcomes. In one trial comparing PUFAs with MUFAs (40 participants), there were no serious adverse events; based on low-certainty evidence. In two trials comparing different PUFAs (omega-3 versus omega-6), there may be little to no difference in relapses (RR 1.02, 95% CI 0.62 to 1.66; 2 studies, 129 participants; 30% in the omega-3 versus 29% in the omega-6 group; low-certainty evidence). Among three trials comparing omega-3 with omega-6, there may be little to no difference in change in disability progression, measured as mean change in Expanded Disability Status Scale (EDSS) (mean difference (MD) 0.00, 95% CI -0.30 to 0.30; 3 studies, 166 participants; low-certainty evidence). In one trial comparing omega-3 with omega-6, there was likely no difference in global impression of deterioration (RR 0.99, 95% CI 0.51 to 1.91; 1 study, 86 participants; 29% in omega-3 versus 29% in omega-6 group; moderate-certainty evidence). In one trial comparing omega-3 with omega-6 (86 participants), there was likely no difference in number of new T1- weighted gadolinium-enhancing lesions, based on moderate-certainty evidence. In four trials comparing omega-3 with omega-6, there may be little to no difference in serious adverse events (RR 1.12, 95% CI 0.38 to 3.31; 4 studies, 230 participants; 6% in omega-3 versus 5% in omega-6 group; low-certainty evidence). In four trials examining antioxidant supplementation with placebo, there may be little to no difference in relapses (RR 0.98, 95% CI 0.59 to 1.64; 4 studies, 345 participants; 17% in the antioxidant group versus 17% in the placebo group; low-certainty evidence). In six trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning change in disability progression, measured as mean change of EDSS (MD -0.19, 95% CI -0.49 to 0.11; 6 studies, 490 participants; very low-certainty evidence). In two trials examining antioxidant supplementation with placebo, there may be little to no difference in global impression of deterioration (RR 0.99, 95% 0.50 to 1.93; 2 studies, 190 participants; 15% in the antioxidant group versus 15% in the placebo group; low-certainty evidence). In two trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning difference in gadolinium-enhancing lesions (RR 0.67, 95% CI 0.09 to 4.88; 2 studies, 131 participants; 11% in the antioxidant group versus 16% in the placebo group; very low-certainty evidence). In three trials examining antioxidant supplementation versus placebo, there may be little to no difference in serious adverse events (RR. 0.72, 95% CI 0.17 to 3.08; 3 studies, 222 participants; 3% in the antioxidant group versus 4% in the placebo group; low-certainty evidence). AUTHORS' CONCLUSIONS There are a variety of controlled trials addressing the effects of dietary interventions for MS with substantial variation in active treatment, comparator, and outcomes of interest. PUFA administration may not differ when compared to alternatives with regards to relapse rate, disability worsening, or overall clinical status in people with MS, but evidence is uncertain. Similarly, at present, there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS-related outcomes.
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Role of Oxidative Stress and Antioxidants in Autism.
Manivasagam, T, Arunadevi, S, Essa, MM, SaravanaBabu, C, Borah, A, Thenmozhi, AJ, Qoronfleh, MW
Advances in neurobiology. 2020;:193-206
Abstract
Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders with poorly understood etiology that are defined exclusively on the basis of behavioral observations. This disorder has been linked to increased levels of oxidative stress and lower antioxidant capacity. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Moreover, environmental and genetic risk factors may intensify vulnerability to oxidative stress in autism. Collectively, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease both in terms of pathogenesis and clinical symptoms. Antioxidant supplementation, or ways to improve the altered metabolite levels in the interconnected transmethylation and transsulfuration pathways, has been associated with decreased autistic behaviors and severity. This chapter provides a conceptual framework on oxidative stress and antioxidants utility. These types of interventions should be further studied in order to determine their effectiveness at improving metabolic imbalances.
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[Selenium and zinc: "antioxidants" for healthy aging?].
Steinbrenner, H, Klotz, LO
Zeitschrift fur Gerontologie und Geriatrie. 2020;(4):295-302
Abstract
Selenium and zinc are essential trace elements and an inadequate dietary intake has been implicated in the decline of immune and cognitive functions in aged persons and in the pathogenesis of age-related disorders. Both micronutrients are often marketed as "antioxidants" in mineral supplements; however, neither selenium nor zinc are antioxidants per se but they may exert beneficial effects as components of enzymes and other proteins that catalyze redox reactions and/or are involved in the maintenance of redox homeostasis. According to epidemiological data older individuals have an increased risk of developing deficiencies in the selenium and zinc status; however, such statistical correlations in epidemiological studies do not imply a causal association. Intervention trials are scarce and have yielded inconsistent and sometimes even adverse results. It should also be noted that the observed deficiencies in micronutrients may not necessarily be attributable to inadequate dietary intake as the absorption and distribution within the body might also be influenced by factors such as medications or interaction with other food ingredients. Thus, any dietary supplementation should be implemented with caution and persons who wish to take mineral supplements should first seek medical advice. This article discusses the role of selenium and zinc in biological antioxidant systems, summarizes findings on the supply and supplementation of aged persons with these trace elements and on the influence they may exert on aging-related health issues, such as cognitive decline and type 2 diabetes mellitus.