Use Of Antioxidant Supplements Research Articles

N-acetyl cysteine (NAC) administration induces behavioral abnormalities in mice experiencing proteotoxic cardiac disease

Background: The co-occurrence of cardiac and neurological complications is becoming increasingly common among individuals diagnosed with either of these disorders. Hypothesis: We tested the hypothesis that elevating glutathione (GSH) levels through N-acetyl cysteine (NAC), a precursor for GSH synthesis, leads to behavioral abnormalities in a mouse model with proteotoxic heart disease. Approach: We used a transgenic mouse model expressing a cardiac-specific human mutant R120G-αB-crystallin (hR120GCryAB-TG), which develops progressive heart failure due to proteotoxicity. Our investigation aimed to understand the effects of NAC on brain redox and behavior in this model. Results: Administering NAC for a period of 12 weeks, we observed an increase in glutathione levels and its redox state (GSH/GSSG) in both heart (1.0 vs. 3.0 Fold in NTG vs. TG; p>0.001) and brain (1.0 vs. 4.0 Fold in NTG vs. TG; p>0.01) tissues. Interestingly, this increase was associated with exacerbated cardiac dysfunction and abnormal behavior. The administration of NAC worsened both structural and functional defects in the hearts of the transgenic (TG) mice, indicating that enhancing antioxidant defense mechanisms could trigger proteotoxic insults through reductive stress (RS). Additionally, the brain of TG mice exhibited enhanced reductive capacity (p>0.01), accompanied by significant alterations in the levels of Tau and α-Synuclein proteins, when compared to non-transgenic (NTG) mice. While NTG mice, with or without NAC treatment, displayed normal behavior, TG mice treated with NAC developed severe behavioral abnormalities, including cognitive impairment (p>0.01). Conclusions: These findings suggest that increased GSH levels (i.e. RS) in progressive heart failure could cause behavioral issues. Thus, further research into the underlying redox mechanisms in other organs, including the brain, is necessary to better understand the use of antioxidant supplements for heart failure treatment. This study will aid in developing personalized therapeutic strategies. National Institute of Health - NHLBI R01 (R01-2RHL118067; Namakkal-Soorappan) American Heart Assocaition (20POST35200085; Sunny). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

P-084 Oral antioxidant supplementation ameliorates the deleterious effects of plasticizers Bisphenol AF (BPAF) and Dibutyl Phthalate (DBP) on mouse sperm DNA integrity

Abstract Study question Do common chemicals in plastic, BPAF and DBP, negatively impact sperm parameters and DNA integrity, and can oral antioxidant supplementation mitigate their impact? Summary answer Short-term, low-dose exposure to BPAF or DBP did not impact testicular/epididymal histology but caudal epididymal sperm parameters, particularly DNA integrity was significantly compromised. What is known already Plasticizers are among the most commonly produced chemicals worldwide with 90% of people showing detectable levels in their urine. As endocrine disruptors (EDCs), they act as estrogen mimetics but can also induce oxidative stress and form DNA adducts. Numerous studies have linked exposure to EDCs to impaired spermatogenesis, sperm DNA damage and male infertility. Limited studies suggest antioxidants may alleviate the reproductive toxicity of EDCs. This study measured the effects of short-term exposures to two common environmental EDCs (BPAF & DBP) on the post-testicular compartment epididymis and investigate the efficacy of an oral antioxidant supplement to safeguard sperm DNA integrity. Study design, size, duration Adult male CD1 mice were exposed to low doses (50mg/kg) of BPAF or DBP with or without co-administration of antioxidant supplementation (Fertilix®) for 14 days and evaluated after euthanasia. Participants/materials, setting, methods All experiments were performed at the University Clermont Auvergne, Clermont-Ferrand, France. Mice were supplemented with BPAF, DBP or/and Fertilix® in their drinking water. The results of exposure of males were evaluated against controls and included: testicular and epididymal histology, epididymal ROS status via 4-HNE levels in caput protein extracts, general semen parameters: (count, motility, viability, acrosome integrity), sperm nuclear/DNA parameters [decondensation (Toluidine blue stain), fragmentation (TUNEL test), oxidation (8-OHdG residue level)]. Main results and the role of chance The histology of the testis and epididymis was unaffected by the exposure conditions used. An oxidative stress situation was evident by the EDC exposures, demonstrated by increased level of 4-HNE adducts in the epididymal caput protein extracts. Viability, total and progressive motility, and acrosome integrity of caudal epididymal spermatozoa remained unaltered in exposed animals compared with controls. Exposure to BPAF but not DBP significantly decreased sperm count. Sperm nuclear/DNA integrity assessed by the percentages of sperm with decondensed and oxidized nuclei was significantly increased in EDC-exposed animals. Sperm DNA fragmentation did not significantly increase in any group of exposed animals. Co-administration with Fertilix® significantly corrected the defective sperm parameters (nuclear decondensation and DNA base oxidation) with the exception of sperm count which did not return to control levels in BPAF+ Fertilix® treated animals. These data confirm that even at low doses and short-term exposures, epididymal spermatozoa are susceptible to DNA damage induced by environmental ROS-generating EDCs, confirming its association with male infertility. Limitations, reasons for caution The translation of these findings to humans needs to be confirmed, although the nuclear compartment of human sperm is more susceptible to oxidative alterations than that of the mouse. Wider implications of the findings These data demonstrate the susceptibility of post-testicular sperm cells to common environmental chemicals. They also support the use of appropriate antioxidant supplementation as an effective therapeutic choice for individuals with multiple exposures to environmental stressors such as ROS-generating EDCs. Trial registration number not applicable

#2518 EFFECT OF VACCINATION ON OXIDANT/ANTIOXIDANT STATUS IN HEMODIALYSIS PATIENTS WITH POST-COVID CONDITIONS

Abstract Background and Aims Hemodialysis (HD) patients are at high risk for post-COVID conditions and a high mortality rate over a 1-year period after diagnosis of COVID-19, especially in the first 3 months. Evidence shows that vaccinated individuals who experience breakthrough infection are less likely to report post-COVID conditions compared with unvaccinated individuals. Although oxidative stress has been shown to be an important cause of post-COVID conditions, there is a general lack of data on oxidant/antioxidant status in HD patients with post-COVID conditions. The present study aimed to evaluate the oxidant/antioxidant markers in HD patients with post-COVID conditions according to vaccination status. Method A total of 106 HD patients, aged 52.4 ± 10.2 years, and dialysis vintage of 68 (29-134) months, were enrolled in this cross-sectional observational cohort study. Patients were divided into 3 groups according to their vaccination status and the presence of post-COVID conditions. Group 1 consisted of 36 HD patients who had been fully vaccinated against COVID-19 with either Pfizer-BNT-162b2 or Moderna-mRNA-1273 vaccine and had experienced a post-vaccination SARS-CoV-2 infection and had at least 1 post-COVID symptom. Group 2 consisted of 35 fully vaccinated HD patients who had never been infected with COVID-19 (vaccinated control group), and Group 3 included 35 unvaccinated HD patients who had experienced COVID-19 and had post-COVID conditions (unvaccinated control group). Concentrations of malondialdehyde in serum (MDAs) and erythrocytes (MDAe), sulfhydryl groups (SH-groups), serum catalase activity (CTs), serum transferrin and ceruloplasmin levels were determined 3 months after COVID -19 recovery. Data were expressed as a median and interquartile range [Me (Q25-Q75)] and compared with the Kruskal-Wallis test. Results The vaccinated HD patients with post-COVID conditions had the highest concentrations of MDAs and ceruloplasmin, and lower serum levels of CTs and transferrin compared with the vaccinated and unvaccinated control groups (Table 1). Conclusion Our findings suggest a significant oxidative imbalance in HD patients with post-COVID syndrome most likely due to the synergistic effects of the virus and the vaccine. The use of antioxidant supplements might be a possible strategy to treat post-COVID conditions in HD patients.

Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E.

Oxidative stress, a condition characterized by an imbalance between pro-oxidant molecules and antioxidant defense systems, is increasingly recognized as a key contributor to cancer development. This is because the reactive oxygen species (ROS) generated during oxidative stress can damage DNA, proteins, and lipids to facilitate mutations and other cellular changes that promote cancer growth. Antioxidant supplementation is a potential strategy for decreasing cancer incidence; by reducing oxidative stress, DNA damage and other deleterious cellular changes may be attenuated. Several clinical trials have been conducted to investigate the role of antioxidant supplements in cancer prevention. Some studies have found that antioxidant supplements, such as vitamin A, vitamin C, and vitamin E, can reduce the risk of certain types of cancer. On the other hand, some studies posit an increased risk of cancer with antioxidant supplement use. In this review, we will provide an overview of the current understanding of the role of oxidative stress in cancer formation, as well as the potential benefits of antioxidant supplementation in cancer prevention. Additionally, we will discuss both preclinical and clinical studies highlighting the potentials and limitations of preventive antioxidant strategies.

Antioxidant Supplementation in Oxidative Stress-Related Diseases: What Have We Learned from Studies on Alpha-Tocopherol?

Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (α-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on α-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases.

What did we learn in 35 years of research on nutrition and supplements for age-related macular degeneration: a systematic review.

The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on the association between nutrition and antioxidant, vitamin, and mineral supplements and the development or progression of age-related macular degeneration (AMD). The Cochrane Database of Systematic Reviews, Cochrane register CENTRAL, MEDLINE and Embase were searched and studies published between January 2015 and May 2021 were included. The certainty of evidence was assessed according to the GRADE methodology. The main outcome measures were development of AMD, progression of AMD, and side effects. We included 7 systematic reviews, 7 RCTs, and 13 NRS. A high consumption of specific nutrients, i.e. β-carotene, lutein and zeaxanthin, copper, folate, magnesium, vitamin A, niacin, vitamin B6, vitamin C, docosahexaenoic acid, and eicosapentaenoic acid, was associated with a lower risk of progression of early to late AMD (high certainty of evidence). Use of antioxidant supplements and adherence to a Mediterranean diet, characterized by a high consumption of vegetables, whole grains, and nuts and a low consumption of red meat, were associated with a decreased risk of progression of early to late AMD (moderate certainty of evidence). A high consumption of alcohol was associated with a higher risk of developing AMD (moderate certainty of evidence). Supplementary vitamin C, vitamin E, or β-carotene were not associated with the development of AMD, and supplementary omega-3 fatty acids were not associated with progression to late AMD (high certainty of evidence). Research in the last 35 years included in our overview supports that a high intake of specific nutrients, the use of antioxidant supplements and adherence to a Mediterranean diet decrease the risk of progression of early to late AMD.

A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions.

IntroductionAging is a normal, inevitable, irreversible, and progressive process which is driven by internal and external factors. Oxidative stress, that is the imbalance between prooxidant and antioxidant molecules favoring the first, plays a key role in the pathophysiology of aging and comprises one of the molecular mechanisms underlying age-related diseases. However, the oxidative stress theory of aging has not been successfully proven in all animal models studying lifespan, meaning that altering oxidative stress/antioxidant defense systems did not always lead to a prolonged lifespan, as expected. On the other hand, animal models of age-related pathological phenotypes showed a well-correlated relationship with the levels of prooxidant molecules. Therefore, it seems that oxidative stress plays a more complicated role than the one once believed and this role might be affected by the environment of each organism. Environmental factors such as UV radiation, air pollution, and an unbalanced diet, have also been implicated in the pathophysiology of aging and seem to initiate this process more rapidly and even at younger ages.AimThe purpose of this review is to elucidate the role of oxidative stress in the physiology of aging and the effect of certain environmental factors in initiating and sustaining this process. Understanding the pathophysiology of aging will contribute to the development of strategies to postpone this phenomenon. In addition, recent studies investigating ways to alter the antioxidant defense mechanisms in order to prevent aging will be presented.ConclusionsCareful exposure to harmful environmental factors and the use of antioxidant supplements could potentially affect the biological processes driving aging and slow down the development of age-related diseases. Maybe a prolonged lifespan could not be achieved by this strategy alone, but a longer healthspan could also be a favorable target.

A Comprehensive Analysis of the Role of Oxidative Stress in the Pathogenesis and Chemoprevention of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSMF) is a chronic oral potentially malignant disorder (OPMD). It is described as a scarring disease of the oral mucosa associated with excess oxidants and insufficient antioxidants. While it is becoming increasingly accepted that oxidative stress results in excessive accumulation of collagen and progressive fibrosis of the submucosal tissues, there is limited data regarding the moderation of oxidative stress to initiate or prevent OSMF. To assess the scope for mechanism-based approaches to prevent or reverse OSMF, we systematically evaluated the existing literature and investigated the role of oxidative stress in the pathogenesis and chemoprevention of OSMF. A search for relevant articles on PubMed and Scopus was undertaken using pre-defined inclusion and exclusion criteria. A total of 78 articles were selected in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The articles eligible for assessment investigated both OSMF and/or oxidative stress biomarkers or specific antioxidants. Both in vitro and human studies consistently demonstrated variations in oxidative stress biomarker levels in OSMF and revealed an increase in oxidative stress, paralleling the development of the disease. Furthermore, the use of antioxidant supplements was overall associated with an improvement in clinical outcomes. Having identified the significance of oxidative stress in OSMF and the therapeutic potential of antioxidant supplements, this scoping review highlights the need for further well-designed studies in the development of mechanism-based interventions for managing OSMF.

Dietary antioxidant supplements and risk of keratinocyte cancers in women: a prospective cohort study.

Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk. E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40-65years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors. Over 1995-2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15-1.62), particularly with BCC (HR = 1.40, 95% CI 1.17-1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03-1.52) and SCC (HR = 1.43, 95% CI 1.03-1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00-2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake. Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed.

Nutrition implications of intrinsic restrictive lung disease.

Restrictive lung disease is defined as a reduction in lung volume that may be due to intraparenchymal or extraparenchymal causes. Intraparenchymal causes falls under the umbrella term of interstitial lung disease (ILD) and includes idiopathic pulmonary fibrosis. This manuscript provides an overview of ILD and can be beneficial for all clinicians working with patients with ILD. Although not well documented, the prevalence of malnutrition in patients with ILD has been reported to be between ~9% and 55%. Body mass index has been shown to predict survival; but more recently, research has suggested that fat-free mass has a larger influence on survival. There is insufficient evidence to support the use of antioxidant or vitamin supplementation to help diminish the chronic inflammatory process that is seen in this patient population. There are data from studies examining the vitamin D status in this patient population, but research on vitamin D supplementation appears to be lacking. Registered dietitian nutritionists should continue to advocate and play a more prominent role in the nutrition management of patients with ILD as part of standard of care.

EFFECTS OF OCCUPATIONAL EXPOSURE TO IONIZING RADIATION ON OXIDATIVE STRESS AND INFLAMMATORY MARKERS IN HEALTHCARE WORKERS OF A UNIVERSITY HOSPITAL IN KONYA, TURKEY

OBJECTIVE Ionizing radiation (IR) has a wide area of use and its effects on human health have been discussed since its discovery. This study aimed to show oxidative stress and inflammation due to ionizing radiation exposure based on biomarkers in healthcare workers.
 METHOD This study was conducted with 172 people, who were exposed to IR in the work environment and those who did not have exposure to radiation. In this cross-sectional study, a data collection form was used to obtain data from the participants. In addition, 6 ml of blood was taken to measure their tumor necrosis factor (TNF)-alpha, total oxidant status (TOS), interleukin (IL)-10 and total antioxidant status (TAS) levels, and calculate their oxidative stress index (OSI) values.
 RESULTS In the ionizing radiation group, 50% of the participants were men, the mean age was 35.91±7.07 years, and the mean duration of employment was 9.80±7.1 years. The TOS, OSI, TNF-α and IL-10 values were higher and TAS was lower in the ionizing radiation group compared to the participants without exposure to ionizing radiation. Gender, smoking, alcohol use, presence of chronic diseases, regular medication use, antioxidant supplement use, and exposure to radiation for medical diagnosis and treatment within the last year did not affect oxidative stress and inflammation in the radiation workers. The cut-off values of the TOS, TAS, OSI, TNF-α and IL-10 biomarkers were also determined.
 CONCLUSION Occupational low-dose long-term exposure to ionizing radiation was found to increase oxidative stress and inflammation.

The Effect of Q10 Supplementation on Lipid and DNA Degradation Indices Following an Acute Physical Activity

Background and Objectives The use of antioxidant supplements improves and reduces oxidative stress factors following intense intense exercise. Exhaustion was performed in female athletes. Subjects and Methods 14 female athletes with an age range of 20 to 28 years and a maximum oxygen consumption of 42-52 m/kg/min in a quasi-experimental design randomly divided into two groups receiving coenzyme Q10 supplementation and placebo (5 mg/kg body weight). Were. After 14 days of coenzyme Q10 supplementation, the subjects performed an intense, debilitating activity. Urine samples were collected in three stages (baseline, before and 24 hours after exhaustive activity) to determine the concentration of 8-OHdG and MDA. Results There was a significant difference of 62% in the increasing response of urinaryOHdG-8 to an exhausting aerobic exercise session (P = 0.003). However, the 2% difference in the increasing urinary MDA response of the supplement and placebo groups was not significant after the last quasi-competitive aerobic training session (P = 0.7). Conclusion According to the results of the study, two weeks of high-pressure aerobic training causes DNA damage and lipid peroxidation in female athletes, and supplementation with Q10 helps prevent the 8-OHdG response of female athletes after a strenuous high-pressure aerobic training session and reduces DNA damage. Become athlete

Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1

BackgroundControversy over the benefits of antioxidants supplements in cancers persists for long. Using hepatocellular carcinoma (HCC) as a model, we investigated the effects of exogenous antioxidants N-acetylcysteine (NAC) and glutathione (GSH) on tumor formation and growth.MethodsMultiple mouse models, including diethylnitrosamine (DEN)-induced and Trp53KO/C-MycOE-induced HCC models, mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection were used. In vitro assays including ROS assay, colony formation, sphere formation, proliferation, migration and invasion, apoptosis, cell cycle assays were conducted. Western blot was performed for protein expression and RNA-sequencing to identify potential gene targets.ResultsIn these multiple different mouse and cell line models, we observed that NAC and GSH promoted HCC tumor formation and growth, accompanied with significant reduction of intracellular reactive oxygen species (ROS) levels. Moreover, NAC and GSH promoted cancer stemness, and abrogated the tumor-suppressive effects of Sorafenib both in vitro and in vivo. Exogenous supplementation of NAC or GSH reduced the expression of NRF2 and GCLC, suggesting the NRF2/GCLC-related antioxidant production pathway might be desensitized. Using transcriptomic analysis to identify potential gene targets, we found that TMBIM1 was significantly upregulated upon NAC and GSH treatment. Both TCGA and in-house RNA-sequence databases showed that TMBIM1 was overexpressed in HCC tumors. Stable knockdown of TMBIM1 increased the intracellular ROS; it also abolished the promoting effects of the antioxidants in HCC cells. On the other hand, BSO and SSA, inhibitors targeting NAC and GSH metabolism respectively, partially abrogated the pro-oncogenic effects induced by NAC and GSH in vitro and in vivo.ConclusionsOur data implicate that exogenous antioxidants NAC and GSH, by reducing the intracellular ROS levels and inducing TMBIM expression, promoted HCC formation and tumor growth, and counteracted the therapeutic effect of Sorafenib. Our study provides scientific insight regarding the use of exogenous antioxidant supplements in cancers.

The role of antioxidants in the treatment of infertile men with varicocele

Varicocele is a common disease that occurs in 35–40% of men with primary infertility and in 80% of men with secondary infertility Disturbance of microcirculation in the testicles, which occurs during varicocele, lead to ischemia and hypoxia of the testicles, which provoke degenerative changes in all testicular cell populations. Retrograde blood flow from the testicular vein and the external spermatic vein into pampiniform venous plexus leads to an increase of hydrostatic pressure in the testicular vascular system and rise of temperature, and it also contributes to the development of sterile inflammation. Oxidative stress, nitrosative stress, and hypoxia are generally recognized elements of the pathogenesis of infertility associated with varicocele. It is known that when the supraphysiological level of reactive oxygen species in the ejaculate is reached, their concentration disrupts the structure and function of spermatozoa. Nitric oxide (NO) is involved in the regulation of body temperature, NO-dependent mechanisms may contribute to the increased scrotal temperature during varicocele. The physiological concentration of NO pro duced by testicular macrophages stimulates steroidogenesis in Leydig cells. However, in the presence of certain reactive oxygen species, NO can transform into peroxynitrite and other strong cytotoxic metabolites, which lead to dysregulation of testosterone synthesis involved in spermatogenesis. Also, manifestations of varicocele among infertile men have decreased expression levels of the testis-specific heat-shock protein, HSPA2, and abnormal methylation of sperm DNA. Therefore, the use of combined anti oxidant supplements as part of adjuvant therapy after surgical treatment or as an independent application in some clinical cases appears to be an adequate strategy to optimize fertility in patients with varicocele. In this review, we evaluated the importance of various antioxidants, such as vitamin E, folic acid, carnitine, inositol, arginine, acetylcysteine, zinc, selenium in spermatogenesis and their effect on reproductive function during varicocele.

P–022 Improvement in sperm concentration and motility after oral antioxidant supplementation in infertile men with varicocele who have not undergone surgical repair: systematic review and meta-analys

Abstract Study question Does oral antioxidant supplementation improve sperm quality in infertile men with varicocele who have not undergone surgical repair? Summary answer Oral antioxidant supplementation improves sperm concentration and motility in infertile men with varicocele who have not undergone surgical repair. What is known already: Benefit from oral antioxidant supplementation has been shown in infertile men with varicocele following surgical repair. Similarly, oral antioxidant supplementation has been suggested in infertile men with varicocele who have not undergone surgical repair. However, its effect currently remains controversial. Study design, size, duration A literature search was performed until January 2021 aiming to identify prospective studies evaluating the use of oral antioxidant supplementation alone or in combination in men with varicocele who have not undergone surgical repair. Participants/materials, setting, methods Seven prospective studies were identified, published between 1987 and 2018, including 278 infertile men with varicocele who had not undergone surgical repair. The number of patients included ranged from 20 to 65. Sperm analysis, evaluating sperm concentration, motility and morphology was performed in these studies before and after oral antioxidant supplementation. Meta-analysis of weighted data was performed using random effects model. Results are reported as weighted mean difference (WMD) with 95% confidence interval (CI). Main results and the role of chance Seven studies were included in the systematic review. Oral antioxidant supplementation was performed by a combination of pentoxifylline, zinc and folic acid (single study), a combination of l-carnitine, fumarate, acetyl-l-carnitine, fructose, CoQ, vitamin C, zinc, folic acid and vitamin B12 (single study), a combination of L-Carnitine, vitamin C, coenzyme Q10, vitamin E, vitamin B9, vitamin B12, zinc , and selenium, l-carnitine (single study), or sole treatment with acetyl-l-carnitine (single study), L-Carnitine (single study), Coenzyme Q10 (single study) or zinc sulfate (single study). For the purpose of meta-analysis, the effect of oral antioxidant supplementation was evaluated after three months of treatment. Oral antioxidant supplementation significantly increased sperm concentration (WMD +5.65x106/ml 95% CI: +1.11 to + 10.12 p = 0.01, random effects model) and motility (WMD +4.30%, 95% CI: +0.86 to + 7.74 p = 0.01, random effects model) in infertile men with varicocele who had not undergone surgical repair. On the other hand, no significance difference was observed in sperm morphology (WMD +3.9%, 95% CI: –0.16 to + 8.04 p = 0.06, random effects model) and volume (WMD +0.53ml, 95% CI: 0.0 to + 1.0 p = 0.052, random effects model). Limitations, reasons for caution The number of relevant trials and that of patients included is small to allow for solid conclusions to be drawn. Moreover, although different oral antioxidants have been administered in infertile who had not undergone surgical repair, subgroup analysis was not feasible. Wider implications of the findings: Currently, limited evidence supports the use of oral antioxidants in the treatment of men with varicocele, who have not undergone surgical repair. Although the benefit in sperm concentration and motility appears to be modest, it might be important regarding achievement of pregnancy in these men. Trial registration number Not applicable

A Brief Overview of Oxidative Stress in Adipose Tissue with a Therapeutic Approach to Taking Antioxidant Supplements.

One of the leading causes of obesity associated with oxidative stress (OS) is excessive consumption of nutrients, especially fast-foods, and a sedentary lifestyle, characterized by the ample accumulation of lipid in adipose tissue (AT). When the body needs energy, the lipid is broken down into glycerol (G) and free fatty acids (FFA) during the lipolysis process and transferred to various tissues in the body. Materials secreted from AT, especially adipocytokines (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)) and reactive oxygen species (ROS), are impressive in causing inflammation and OS of AT. There are several ways to improve obesity, but researchers have highly regarded the use of antioxidant supplements due to their neutralizing properties in removing ROS. In this review, we have examined the AT response to OS to antioxidant supplements focusing on animal studies. The results are inconsistent due to differences in the study duration and diversity in animals (strain, age, and sex). Therefore, there is a need for different studies, especially in humans.

Plasma Total Thiols and Total Thiol/Albumin Ratio in Patients Suffering from Depression

Introduction: Increased oxidative stress has been reported in patients who suffer from depressive disorders. Albumin acts as a target for plasma protein oxidation during oxidative stress. The plasma thiols act as significant in vivo antioxidants. Major SH-groups are found on the surface of albumin molecules. Since depressive disorders are related to oxidative stress. Only a few studies have been done that correlate plasma total thiols with major depressive disorder. The authors intended to draw a relationship between oxidative stress, thiols and major depressive disorder by estimating total plasma thiols and calculating the ratio of thiol/albumin. The study may throw some light in understanding whether the use of anti-oxidant supplements to counter oxidative stress in depressed patients. Aim: The aims was to estimate plasma thiols, albumin and obtain a plasma thiol/albumin ratio in people suffering from depression and compare the levels with the control group. Materials and Methods: This case control study was conducted in Kasturba Medical College, Manipal. Plasma thiols were estimated using Ellman’s method. Plasma albumin levels were estimated using Bromo-cresol green dye binding method. Mann- Whitney U test was used for analysing the data for total thiols and thiol/albumin ratio. A p-value <0.05 was considered significant. Results: The study group was made up of 43 (22 males and 21 females) patients and the control group was made up of 40 (18 males and 22 females) healthy controls. Plasma thiol levels and the plasma total thiol/albumin ratio were significantly elevated (p-value=0.00036) in cases (depression) as compared to that of the controls. Conclusion: Plasma total thiols can be used as an early marker for understanding the risk for major depressive disorders and also be used as a prognostic indicator in the follow up of patients suffering from major depressive disorder who are under treatment.

High-altitude hypoxia induced reactive oxygen species generation, signaling, and mitigation approaches.

Homeostasis between pro-oxidants and anti-oxidants is necessary for aerobic life, which if perturbed and shifted towards pro-oxidants results in oxidative stress. It is generally agreed that reactive oxygen species (ROS) production is accelerated with mountainous elevation, which may play a role in spawning serious health crisis. Exposure to increasing terrestrial altitude leads to a reduction in ambient O2 availability in cells producing a series of hypoxic oxidative stress reactions and altering the redox balance in humans. Enormous literature on redox signaling drove research activity towards understanding the role of oxidative stress under normal and challenging conditions like high-altitude hypoxia which grounds for disturbed redox signaling. Excessive ROS production and accumulation of free radicals in cells and tissues can cause various pulmonary, cardiovascular, and metabolic pathophysiological conditions. In order to counteract this oxidative stress and maintain the balance of pro-oxidants and anti-oxidants, an anti-oxidant system exists in the human body, which, however, gets surpassed by elevated ROS levels, but can be strengthened through the use of anti-oxidant supplements. Such cumulative studies of fundamentals on a global concept like oxidative stress and role of anti-oxidants can act as a foundation to further smoothen for researchers to study over health, disease, and other pathophysiological conditions. This review highlights the interconnection between high altitude and oxidative stress and the role of anti-oxidants to protect cells from oxidative damages and to lower the risk of altitude-associated sickness.

Oxidative Stress in Parkinson's Disease: Potential Benefits of Antioxidant Supplementation.

Parkinson's disease (PD) occurs in approximately 1% of the population over 65 years of age and has become increasingly more common with advances in age. The number of individuals older than 60 years has been increasing in modern societies, as well as life expectancy in developing countries; therefore, PD may pose an impact on the economic, social, and health structures of these countries. Oxidative stress is highlighted as an important factor in the genesis of PD, involving several enzymes and signaling molecules in the underlying mechanisms of the disease. This review presents updated data on the involvement of oxidative stress in the disease, as well as the use of antioxidant supplements in its therapy.

The Role of Antioxidants in the Prevention of Cadmium-Induced Endothelial Dysfunction.

Cadmium is a worldwide spread toxicant that accumulates in tissues and affects many organs, mainly through oxidative damage. Oxidative stress is often associated with cardiovascular diseases and, when it affects vessels, it induces endothelial dysfunction, which, in turn, could precipitate atherosclerosis and hypertension. Therefore, it is reasonable to suggest antioxidant supplementation as a therapy against cadmiuminduced endothelial dysfunction. This literature review aims to present the mechanisms involving oxidative stress in which cadmium induces endothelial dysfunction and the benefits of antioxidant supplementation as a therapeutic strategy against its harmful effects. On PubMed Central, articles that contemplated studies on cadmium intoxication and associated oxidative stress with endothelial dysfunction as well as articles that reported the use of antioxidant supplementation in an attempt to prevent or avoid endothelial dysfunction induced by cadmium exposure were selected. Most of the studies that associated cadmium intoxication with endothelial dysfunction suggested oxidative stress as the major mechanism for this damage. Furthermore, experimental studies also revealed that the administration of substances with antioxidant properties, such as ascorbic acid and curcumin, has beneficial effects on the prevention of such dysfunction, reducing reactive oxygen species within the vessels, preventing a reduction in the amount of glutathione and the increase in blood pressure observed in animals exposed to cadmium. Antioxidant therapy demonstrated to be a potential treatment to reduce cardiovascular injuries provoked by cadmium, but more studies are needed to determine the best antioxidant substance and dose to treat or avoid this complication.