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1.
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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2.
Galacto-oligosaccharides supplementation in prefrail older and healthy adults increased faecal bifidobacteria, but did not impact immune function and oxidative stress.
Wilms, E, An, R, Smolinska, A, Stevens, Y, Weseler, AR, Elizalde, M, Drittij, MJ, Ioannou, A, van Schooten, FJ, Smidt, H, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3019-3031
Abstract
BACKGROUND & AIMS Ageing is associated with an increased risk of frailty, intestinal microbiota perturbations, immunosenescence and oxidative stress. Prebiotics such as galacto-oligosaccharides (GOS) may ameliorate these ageing-related alterations. We aimed to compare the faecal microbiota composition, metabolite production, immune and oxidative stress markers in prefrail elderly and younger adults, and investigate the effects of GOS supplementation in both groups. METHODS In a randomised controlled cross-over study, 20 prefrail elderly and 24 healthy adults received 21.6 g/day Biotis™ GOS (containing 15.0 g/day GOS) or placebo. Faecal 16S rRNA gene-based microbiota and short-chain fatty acids were analysed at 0, 1 and 4 weeks of intervention.Volatile organic compounds were analysed in breath, and stimulated cytokine production, CRP, malondialdehyde, trolox equivalent antioxidant capacity (TEAC) and uric acid (UA) in blood at 0 and 4 weeks. RESULTS Principle coordinate analysis showed differences in microbial composition between elderly and adults (P≤0.05), with elderly having lower bifidobacteria (P≤0.033) at baseline. In both groups, GOS affected microbiota composition (P≤0.05), accompanied by increases in bifidobacteria (P<0.001) and decreased microbial diversity (P≤0.023). Faecal and breath metabolites, immune and oxidative stress markers neither differed between groups (P ≥ 0.125) nor were affected by GOS (P ≥ 0.236). TEAC values corrected for UA were higher in elderly versus adults (P<0.001), but not different between interventions (P ≥ 0.455). CONCLUSIONS Elderly showed lower faecal bifidobacterial (relative) abundance than adults, which increased after GOS intake in both groups. Faecal and breath metabolites, parameters of immune function and oxidative stress were not different at baseline, and not impacted by GOS supplementation. CLINICALTRIALS. GOV WITH STUDY ID NUMBER NCT03077529.
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3.
The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study.
Cojic, M, Kocic, R, Klisic, A, Kocic, G
Frontiers in endocrinology. 2021;:610893
Abstract
Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic "sterile" inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.
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4.
Health disparities: Intracellular consequences of social determinants of health.
Emeny, RT, Carpenter, DO, Lawrence, DA
Toxicology and applied pharmacology. 2021;:115444
Abstract
Health disparities exist dependent on socioeconomic status, living conditions, race/ethnicity, diet, and exposures to environmental pollutants. Herein, the various exposures contributing to a person's exposome are collectively considered social determinants of health (SDOH), and the SDOH-exposome impacts health more than health care. This review discusses the extent of evidence of the physiologic consequences of these exposures at the intracellular level. We consider how the SDOH-exposome, which captures how individuals live, work and age, induces cell processes that modulate a conceptual "redox rheostat." Like an electrical resistor, the SDOH-exposome, along with genetic predisposition and age, regulate reductive and oxidative (redox) stress circuits and thereby stimulate inflammation. Regardless of the source of the SDOH-exposome that induces chronic inflammation and immunosenescence, the outcome influences cardiometabolic diseases, cancers, infections, sepsis, neurodegeneration and autoimmune diseases. The endogenous redox rheostat is connected with regulatory molecules such as NAD+/NADH and SIRT1 that drive redox pathways. In addition to these intracellular and mitochondrial processes, we discuss how the SDOH-exposome can influence the balance between metabolism and regulation of immune responsiveness involving the two main molecular drivers of inflammation, the NLRP3 inflammasome and NF-κB induction. Mitochondrial and inflammasome activities play key roles in mediating defenses against pathogens and controlling inflammation before diverse cell death pathways are induced. Specifically, pyroptosis, cell death by inflammation, is intimately associated with common disease outcomes that are influenced by the SDOH-exposome. Redox influences on immunometabolism including protein cysteines and ion fluxes are discussed regarding health outcomes. In summary, this review presents a translational research perspective, with evidence from in vitro and in vivo models as well as clinical and epidemiological studies, to outline the intracellular consequences of the SDOH-exposome that drive health disparities in patients and populations. The relevance of this conceptual and theoretical model considering the SARS-CoV-2 pandemic are highlighted. Finally, the case of asthma is presented as a chronic condition that is modified by adverse SDOH exposures and is manifested through the dysregulation of immune cell redox regulatory processes we highlight in this review.
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5.
Polyphenols are potential nutritional adjuvants for targeting COVID-19.
El-Missiry, MA, Fekri, A, Kesar, LA, Othman, AI
Phytotherapy research : PTR. 2021;(6):2879-2889
Abstract
The newly emerging severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) is a dangerous pathogen that causes global health problems. It causes a disease called coronavirus disease 2019 (COVID-19) with high morbidity and mortality rates. In SARS-Cov-2-infected patients, elevated oxidative stress and upsurge of inflammatory cytokines are the main pathophysiological events that contribute to the severity and progression of symptoms and death. The polyphenols are natural compounds abundant in fruits and vegetables that are characterized by their high antioxidant and anti-inflammatory effects. Polyphenols have potential as an intervention for preventing respiratory virus infection. The beneficial effects of polyphenols on COVID-19 might be due to multiple mechanisms. Polyphenols can strengthen the body's anti-inflammatory and antioxidant defenses against viral infection. Targeting virus proteins and/or blocking cellular receptors are other plausible antiviral approaches to prevent the entry of the virus and its replication in the host cells. The results on the antiviral effects of various polyphenols, especially on SARS-CoV-2, are promising. The aim of this review is to clarify the role of polyphenols in strengthening antioxidant defenses and upregulating the immune systems of COVID-19 patients and to prevent replication and spreading of the virus.
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6.
Can Endometriosis-Related Oxidative Stress Pave the Way for New Treatment Targets?
Cacciottola, L, Donnez, J, Dolmans, MM
International journal of molecular sciences. 2021;(13)
Abstract
Endometriosis is a disease of reproductive age characterized by chronic pelvic pain and infertility. Its pathogenesis is complex and still partially unexplained. However, there is increasing evidence of the role of chronic inflammation, immune system dysregulation, and oxidative stress in its development and progression. The latter appears to be involved in multiple aspects of the disease. Indeed, disease progression sustained by a hyperproliferative phenotype can be related to reactive oxygen species (ROS) imbalance, as numerous experiments using drugs to counteract hyperproliferation have shown in recent years. Chronic pelvic pain is also associated with cell function dysregulation favoring chronic inflammation and oxidative stress, specifically involving macrophages and mast cell activation. Moreover, there is increasing evidence of a role for ROS and impaired mitochondrial function not only as deleterious effectors of the ovarian reserve in patients with endometriomas but also in terms of oocyte quality and, hence, embryo development impairment. Targeting oxidative stress looks to be a promising strategy to both curb endometriotic lesion progression and alleviate endometriosis-associated symptoms of chronic pain and infertility. More investigations are nevertheless needed to develop effective therapeutic strategies for clinical application.
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7.
Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis.
Iddir, M, Brito, A, Dingeo, G, Fernandez Del Campo, SS, Samouda, H, La Frano, MR, Bohn, T
Nutrients. 2020;(6)
Abstract
The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.
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8.
Colorimetric analysis of the early oxidation of dopamine by hypochlorous acid as preliminary screening tool for chemical determinants of neuronal oxidative stress.
Palladino, P, Torrini, F, Scarano, S, Minunni, M
Journal of pharmaceutical and biomedical analysis. 2020;:113016
Abstract
The hypochlorous acid produced by the innate immune system during inflammation characteristic of several neurodegenerative disorders is responsible for the generation of chlorinated byproducts of dopamine in neurons where this neurotransmitter reaches the highest concentration. Therefore, this physiological acid could play a key role in neuronal oxidative stress associated to aberrant dopamine-quinones (DQ) production. Here we report a model study simulating simplified conditions of HOCl reaction with dopamine (DA) in neurons, showing for the first time that DA is immediately converted by HOCl to the yellow colored DQ molecule. The DQ originated from dopamine oxidation results directly proportional to the total amount of the oxidant with excellent reproducibility. Furthermore, following the several evidences of the interplay between cytosolic dopamine and calcium in neurodegenerative disorders, we have verified that the presence of calcium cation influences the dopamine oxidation pathway likely due to the metal chelation by semiquinone formed in the early stage of dopamine oxidation. This experimental approach, based on the isolation of the highly reactive DQ molecule, could be useful for prelaminar investigation of the (putative) determinants of dopamine-poisoning derivatives formation.
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9.
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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10.
Inflammation and Mitochondrial Dysfunction in Autism Spectrum Disorder.
Gevezova, M, Sarafian, V, Anderson, G, Maes, M
CNS & neurological disorders drug targets. 2020;(5):320-333
Abstract
Autism Spectrum Disorders (ASD) is a severe childhood psychiatric condition with an array of cognitive, language and social impairments that can significantly impact family life. ASD is classically characterized by reduced communication skills and social interactions, with limitations imposed by repetitive patterns of behavior, interests, and activities. The pathophysiology of ASD is thought to arise from complex interactions between environmental and genetic factors within the context of individual development. A growing body of research has raised the possibility of identifying the aetiological causes of the disorder. This review highlights the roles of immune-inflammatory pathways, nitro-oxidative stress and mitochondrial dysfunctions in ASD pathogenesis and symptom severity. The role of NK-cells, T helper, T regulatory and B-cells, coupled with increased inflammatory cytokines, lowered levels of immune-regulatory cytokines, and increased autoantibodies and microglial activation is elucidated. It is proposed that alterations in mitochondrial activity and nitrooxidative stress are intimately associated with activated immune-inflammatory pathways. Future research should determine as to whether the mitochondria, immune-inflammatory activity and nitrooxidative stress changes in ASD affect the development of amygdala-frontal cortex interactions. A number of treatment implications may arise, including prevention-orientated prenatal interventions, treatment of pregnant women with vitamin D, and sodium butyrate. Treatments of ASD children and adults with probiotics, sodium butyrate and butyrate-inducing diets, antipurinergic therapy with suramin, melatonin, oxytocin and taurine are also discussed.