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Diet-Derived Circulating Antioxidants and Risk of Stroke: A Mendelian Randomization Study.
Miao, R, Li, J, Meng, C, Li, Y, Tang, H, Wang, J, Deng, P, Lu, Y
Oxidative medicine and cellular longevity. 2022;:6457318
Abstract
BACKGROUND Oxidative stress is crucial in stroke pathogenesis. Many cohort-based studies suggested that the intake of exogenous antioxidants originated from food may prevent stroke. However, the corresponding randomized controlled trials did not show diet-derived antioxidants have a protective effect on stroke. OBJECTIVES To examine the association of genetically proxied diet-derived antioxidants with stroke risk using Mendelian randomization. METHODS We performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of diet-derived antioxidants on stroke risk. For exposure data, we extracted genetic variants as instrumental variables (IVs) that are strongly associated with frequently used diet-derived antioxidants, including vitamin C, vitamin E (α-tocopherol, γ-tocopherol), carotene, retinol, zinc, and selenium, from a large-scale genome-wide association study (GWAS). We obtained IVs' corresponding effect estimates on the risk of total stroke and ischemic stroke from a GWAS meta-analysis with 40,585 cases and 406,111 controls. Finally, we applied five types of Mendelian randomization analysis to obtain preliminary MR results and performed four three kinds of sensitivity analysis to verify them. RESULTS According to the primary MR estimations and further sensitivity analyses, we established two robust associations after Bonferroni correction: genetically proxied circulating γ-tocopherol was causally associated with total stroke [odds ratio (OR) = 0.68, 95% confidence interval (CI) (0.52-0.88), p = 3.78E - 03] and ischemic stroke [OR = 0.66, 95% CI (0.51-0.86), p = 2.34E - 03]. There was no evidence to support the causal effect of other diet-derived antioxidants on the risk of total stroke and ischemic stroke. CONCLUSION Our study revealed a protective impact of genetic susceptibility to high circulating γ-tocopherol levels on stroke risk, providing new information on the potential therapeutic targets for primary stroke prevention.
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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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An Evaluation of Oxidative Stress With Thiol/Disulfide Homeostasis in Patients With Persistent Allergic Rhinitis.
Göker, AE, Alagöz, MH, Kumral, TL, Karaketir, S, Yilmazer, AB, Tutar, B, Ahmed, EA, Biçer, C, Uyar, Y
Ear, nose, & throat journal. 2022;(1):NP13-NP17
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Abstract
BACKGROUND We evaluated the efficacy of medical treatment on thiol-disulfide balance despite ongoing allergic stimulation. METHODS The research design was a prospective observational study that included 35 persistent allergic rhinitis (AR) patients. All patients who were diagnosed with persistent AR were included. A skin prick test was applied to all patients, and the Sino-nasal Outcome Test-22 was used to evaluate sinonasal symptoms. Thiol/disulfide homeostasis balance parameters were measured using a novel automatic and spectrophotometric method and compared statistically. Serum total thiol (TT), native thiol (SH), disulphide (SS), disulphide/native thiol (SS/SH), disulphide/total thiol (SS/TT), and native thiol/total thiol (SH/TT) ratios were measured after the second month of the treatment. RESULTS The 35 patients included 20 (58%) females and 15 (42%) males. The mean age of the patients was 33.17 ± 9.9 years. Disulphide, SS/SH, and SS/TT ratios decreased significantly after the treatment (P < .05), while SH and SH/TT increased significantly (P < .05). The mean SH measurement increased significantly in the second month (P = .001), but TT mean measurements showed no difference after the treatment (P = .058). The mean SS measurements, on the other hand, decreased significantly in the second month (P = .003). CONCLUSION Thiol/disulfide homeostasis may be used as a marker to evaluate the efficacy of persistent AR treatments. After the treatment, the increase in SH levels suggested the decrease in oxidative stress, even though allergen exposure continued.
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Oxidative stress and motion sickness in one crew during competitive offshore sailing.
Giacon, TA, Bosco, G, Vezzoli, A, Dellanoce, C, Cialoni, D, Paganini, M, Mrakic-Sposta, S
Scientific reports. 2022;(1):1142
Abstract
Competitive Offshore Ocean Sailing is a highly demanding activity in which subjects are exposed to psychophysical stressors for a long time. To better define the physiological adaptations, we investigated the stress response of subjects exposed to 3-days long ocean navigation with disruption of circadian rhythms. 6 male subjects were involved in the study and provided urine and saliva samples before setting sail, during a single day of inshore sailing, during 3-days long ocean navigation, and at the arrival, to measure oxidative stress, cortisol, nitric oxide metabolites (NOx) and metabolic response. Motion Sickness questionnaires were also administered during the navigation. The crew suffered a mean weight loss of 1.58 kg. After the long navigation, a significant increase in ROS production and decrease in total antioxidant capacity and uric acid levels were observed. Lipid peroxidation, NO metabolites, ketones, creatinine, and neopterin levels were also increased. Furthermore, a significant increase in cortisol levels was measured. Finally, we found a correlation between motion sickness questionnaires with the increase of NOx, and no correlation with cortisol levels. Physical and psychological stress response derived from offshore sailing resulted in increased oxidative stress, nitric oxide metabolites, and cortisol levels, unbalanced redox status, transient renal function impairment, and ketosis. A direct correlation between motion sickness symptoms evaluated through questionnaires and NOx levels was also found.
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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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Vitamin D3 Supplementation Effects on Spermatogram and Oxidative Stress Biomarkers in Asthenozoospermia Infertile Men: a Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.
Maghsoumi-Norouzabad, L, Zare Javid, A, Mansoori, A, Dadfar, M, Serajian, A
Reproductive sciences (Thousand Oaks, Calif.). 2022;(3):823-835
Abstract
The objective is to evaluate the effects of vitamin D3 (VD3) on sperm parameters and seminal and serum oxidative stress (OS) biomarkers in asthenozoospermia infertile men. This randomized, triple-masking, placebo-controlled clinical trial conducted on 86 asthenozoospermia infertile men with serum 25 hydroxy vitamin D3 (25-OH-D3) < 30 ng/ml in the infertility clinic of Ahvaz Jahad Daneshgahi, Iran. Patients were randomly allocated to groups A and B, who received daily 4000 IU vitamin D3 (VD3) and matching placebo respectively for 3 months. Demographic data, dietary intake, physical activity, sun exposure, anthropometric indices, serum and seminal levels of MDA (Malondialdehyde), 8-hydroxy-2- Dioxy Guanosine (8-OHDG), total antioxidant capacity (TAC) and calcium, sperm DNA fragmentation index (DFI), serum 25-OH-D3, parathyroid hormone (PTH), phosphorus, and sperm parameters were assessed. VD3 supplementation had no significant effects on body weight, body mass index (BMI), waist circumference (WC), body fat (BF), 8-OHDG, DFI, semen volume, sperm count, and normal sperm morphology, but increased post-intervention mean and mean change of serum 25-OH-D3 (P < 0.001, P < 0.001), PTH (P < 0.001, P < 0.001) and phosphorus (P = 0.009, P = 0.049) and seminal calcium (P = 0.035, P = 0.038) and serum calcium (P = 0.008, P = 0.009), seminal TAC (P < 0.001, P < 0.001), and serum TAC (P = 0.007, P = 005), total sperm motility (P < 0.001, P < 0.001) and progressive sperm motility (P < 0.001, P < 0.001) and decreased seminal MDA (P = 0.017, P = 0.004) and serum MDA (P = 006, P = 0.005) significantly compared to the baseline and placebo group respectively. VD3 supplementation may modulate OS and affect sperm motility in men with asthenozoospermia and serum 25-OH-D3 < 30 ng/ml. Iran Clinical Trials Registry, ID: IRCT20151128025274N4, registered on 28 March 2018, URL of trial registry record: https://www.irct.ir/trial/29983.
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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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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.