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The present prospective cohort study aimed to determine whether dietary antioxidants were associated with incident type 2 diabetes mellitus (T2DM). Another objective was to find out whether such associations could be modified by the BMI status. A total of 2188 Tehranian adults aged 21–84 years, free of T2DM with the validated FFQ, was entered in the study. Multivariable Cox proportional hazards models adjusting for confounders were used to assess the association between dietary antioxidants and incident T2DM in total population, as well as in subjects with various BMI statuses. During 8·9 (8·1–9·6) years of follow-up, dietary vitamin E significantly decreased the incident T2DM, after adjustment for confounders. However, other dietary antioxidants were not shown to be significantly associated with incident T2DM. The interaction between dietary vitamin E, Mg and BMI status was found to influence the risk of T2DM (P for interaction < 0·05). After stratification of subjects based on BMI status, it was found that vitamin E and Mg decreased the risk of T2DM only among normal-weight individual. Also, an inverse association was found among dietary vitamin C, dietary Zn and the risk of T2DM in individuals with normal weight but not in overweight and obese individuals; however, the interaction test tended to be significant for these dietary variables. Dietary antioxidants including vitamin E, vitamin C, Zn and Mg when accompanied by healthy weight, may bring benefits to the prevention of T2DM. [ABSTRACT FROM AUTHOR]

Liver diseases are complex conditions, significantly influenced by oxidative stress. This comprehensive review assesses the therapeutic role of antioxidants like l-ascorbic acid and α tocopherol, beta-carotene, various minerals, and plant-based ingredients in mitigating oxidative stress-induced liver diseases. The manuscript delves into the critical influence of genetic and epigenetic factors on disease susceptibility, progression, and response to antioxidant therapy. While animal studies suggest antioxidant efficacy in liver disease treatment, human trials remain inconclusive, and caution is advised due to its possible potential pro-oxidant effects. Moreover, the interactions of antioxidants with other drugs necessitate careful consideration in the management of polypharmacy in liver disease patients. The review underscores the need for further research to establish the clinical benefits of antioxidants with understanding of possible antioxidant toxicities to elucidate the intricate interplay of genetic, epigenetic, and environmental factors in liver diseases. The aim is to foster a better understanding of the knowledge on hepatic disease management with judicial antioxidant therapies. [ABSTRACT FROM AUTHOR]

The excessive and uncontrolled use of pyrethroids, such as cypermethrin (CP), for pest control in Nigeria could adversely affect humans. This study aimed to investigate the oxidative stress response to cypermethrin exposure, focusing on measuring the parameters (i.e., malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)) and the potential therapeutic effects of single and co-administration of ascorbate and alpha-tocopherol. The lungs and hearts of the animals were histologically examined for cypermethrin-induced cytopathic changes. Twenty-five adult male Wistar rats weighing 180–200 g were randomly assigned to five groups, each consisting of five animals. Group I was the control group that was not subjected to any treatment. Group II was orally exposed to cypermethrin at a dosage of 10 mg/kg bw without any additional treatment. Groups III, IV, and V received cypermethrin at standard doses of 10 mg/kg bw and were orally administered with ascorbate (5,000 mg/kg bw), alpha-tocopherol (3,000 mg/kg bw), and a coadministration of ascorbate (5,000 mg/kg bw) and alpha-tocopherol (3,000 mg/kg bw), respectively. The animals were euthanized after 28 days, and samples were processed for histological analysis using hematoxylin and eosin staining. Analysis of variance (ANOVA) and Duncan's multiple range test were used to compare categorical variables of the biochemical parameters and determine the levels of MDA, SOD, GPx, and CAT. The data analysis revealed that the cypermethrin-exposed, untreated rats had elevated MDA levels and a concurrently marked decrease in SOD, GPx, and CAT activities (p<0.05). Additionally, the histopathological examination of the organs indicated inflammation and congestion. The co-administration of ascorbate and alpha-tocopherol restored the biochemical parameters more effectively compared to when the substances were administered individually. In conclusion, co-administration of ascorbic acid and alphatocopherol ameliorates cypermethrin-induced oxidative damage more effectively than a single administration of either substance. This may be due to the synergistic antioxidant properties of the substances. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress inhibits tendon-to-bone healing after rotator cuff repair. Regulation of oxidative stress has the potential to accelerate this healing, but its mechanism remains unclear. Purpose: To investigate the effects of reducing oxidative stress by applying antioxidants, such as N -acetylcysteine (NAC) and vitamin C (VC), on rotator cuff repair in a rat rotator cuff repair model. Study design: Controlled laboratory study. Methods: A total of 48 Sprague Dawley rats underwent bilateral surgery to repair the infraspinatus tendon to its insertion site 1 week after detachment. Rats were assigned to either the NAC group, the VC group, or a control group. Histological evaluation was performed via hematoxylin-eosin or toluidine blue staining, and oxidative stress was assessed via dihydroethidium intensity and protein carbonyl concentration at 3 and 6 weeks. Superoxide dismutase 1 (SOD1), SOD2, SOD3, peroxiredoxin 5, collagen type I (COL1), COL3, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 expression and SOD activity were determined at 3 and 6 weeks. Biomechanical tests were performed at 6 and 12 weeks. Results: Histological evaluation showed that the number of chondrocytes in the NAC group at 6 weeks and in the VC group at 3 and 6 weeks, the area of fibrocartilage at 6 weeks in the VC group, and collagen fibers at 6 weeks in the NAC and VC groups were significantly increased compared with those in the control group. Dihydroethidium intensity at 3 and 6 weeks and protein carbonyls at 6 weeks in the NAC and VC groups were significantly decreased. SOD1 expression and SOD activity at 3 weeks in the VC group and peroxiredoxin 5 expression at 6 weeks in the NAC group were significantly upregulated compared with that in the control group. COL3 expression was significantly upregulated at 6 weeks in the VC group, and MMP-13 expression was significantly decreased at 6 weeks in the NAC and VC groups. The biomechanical strength showed no significant difference. Conclusion: Antioxidant treatment, via NAC or VC administration, reduced oxidative stress in the rotator cuff repair site and accelerated healing. Clinical Relevance: These findings provide essential indications to develop clinical strategies for improved healing after rotator cuff surgical repair in patients. [ABSTRACT FROM AUTHOR]

Background: Among multiple factors that affect the etiology of polycystic ovary syndrome (PCOS), diet has an important contribution. Chronic oxidative stress has also been implicated in the development of PCOS. The present study is an attempt to evaluate dietary total antioxidant capacity (TAC) and its relationship with odds of PCOS in Iran. Materials and Methods: The study was carried out as a case-control study in hospital outpatient clinics, Tehran, Iran. Totally, 310 female participants with a history of PCOS and 602 age-matched controls took part in this study between June 2015 and December 2018. A reproducible and valid 168-item semi-quantitative food frequency inventory was utilized to determine the entire antioxidants of the usual diet in order to calculate dietary TAC. The relationship of dietary TAC with odds of PCOS were assessed adjusting for potential confounders through an estimation of two multivariable conditional regression models. The first tertile was presented as a reference category. Results: In a fully adjusted model, the highest tertile of dietary TAC was associated with a reduced odds of PCOS [odds ratio (OR): 0.81, 95% confidence interval (95% CI): 0.59, 0.96, P for trend: 0.038). In addition, PCOS odds decreased in the highest tertile of α-tocopherol intake (OR: 0.73, 95% CI: 0.56, 0.88, P for trend: 0.023). The adjusted ORs in the highest tertile of vitamin C, β-carotene and magnesium were 0.79 (95% CI: 0.83-0.97), 0.81 (95% CI: 0.67-0.98) and 0.91 (95% CI: 0.55-0.9 8) respectively, with a significant trend. Conclusion: Our results provide evidence that there was a relationship between high TAC diets and lower odds of PCOS. [ABSTRACT FROM AUTHOR]

Background: Benznidazole is an effective drug in the trypanocidal treatment of acute and chronic indeterminate Chagas' disease (CD). However, adverse drug reactions (ADR) are common and frequently cause patients to discontinue treatment.Objectives: We hypothesized that antioxidant supplementation could mitigate benznidazole-induced toxicity.Methods: We co-supplemented an adult traveller with chronic indeterminate CD who experienced benznidazole ADR with ascorbic acid (AA), 1000 mg/day. We measured selected serum biomarkers of oxidative stress [total antioxidant status (TAS), total oxidative status (TOS), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), extracellular glutathione peroxidase (GPX3), catalase (CAT) and total superoxide dismutase (T-SOD)] at timepoints before and throughout benznidazole treatment and after AA co-supplementation.Results: AA co-supplementation effectively mitigated benznidazole-induced ADR during the aetiological treatment of chronic indeterminate CD. The kinetics of serum biomarkers of oxidative stress suggested significantly decreased oxidative insult in our patient.Conclusions: We hypothesize that the key pathophysiological mechanism of benznidazole-associated toxicity is oxidative stress, rather than hypersensitivity. AA co-supplementation may improve adherence to benznidazole treatment of chronic indeterminate (or acute) CD. Oxidative stress biomarkers have the potential to guide the clinical management of CD. Prospective studies are needed to establish the benefit of antioxidant co-supplementation to benznidazole treatment of CD in reducing benznidazole toxicity, parasite clearance and the prevention of end-organ damage. [ABSTRACT FROM AUTHOR]

COVID-19 (COronaVIrus Disease of 2019), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents an ongoing global health challenge and the deadliest epidemic coronavirus outbreak to date. Early sequencing of the viral genome and knowledge from past coronavirus outbreaks (SARS-CoV-1 and Middle East Respiratory Syndrome, MERS) has led to rapid advances in knowledge of how the virus spreads and infects human hosts. Unfortunately, advancing knowledge has not yet produced a treatment that substantially lowers morbidity or mortality and only recently resulted in the development of a vaccine that prevents severe disease. Mounting evidence supports the notion that dietary supplementation of key essential nutrients may contribute to the body's defenses against infection as well as bolster the body's responses to infection. Evidence supporting the potential beneficial roles of vitamin C, vitamin D, zinc, and B3 vitamins is reviewed here, revealing a combination of basic research elucidating underlying mechanisms of action, preclinical studies and human intervention studies has led to the proliferation of registered clinical trials on COVID-19. Overall, the data suggest this collection of nutrients has a promising impact on reducing the risk and/or severity of COVID-19, although firm conclusions await the results of these trials. [ABSTRACT FROM AUTHOR]

Few peculiarities have been observed in the etiology of coronavirus disease 2019 (COVID-19), one such being its greater prevalence in men than women partly due to the higher expressions of angiotensin-converting enzyme-2 (ACE2) in the male reproductive tissues. Recent scientific reports are in line with some of the evidence-based hypotheses in the initial phase of the COVID-19 pandemic, regarding the involvement of oxidative stress (OS) and oxidant-sensitive pathways in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated male reproductive disruptions. The seminal dissemination of SARS-CoV-2 or its components, testicular disruptions due to viral infection and oxidative damage in the testis have all been evidenced recently. High-dose of antioxidants, such as vitamin C, have been shown to be a useful treatment for COVID-19 patients, to alleviate systemic inflammation and OS. In addition, vitamin C is a major testicular antioxidant that neutralizes excess reactive oxygen species (ROS), prevents sperm agglutination, prevents lipid peroxidation, recycles vitamin E, and protects against DNA damage. Thus, the present review aims to discuss the mechanism of COVID-19- mediated male reproductive dysfunctions, based on the evidence available so far, and explore the possibility of using vitamin C in alleviating testicular OS and associated damage caused by COVID-19. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder; affect the metabolism of carbohydrates, proteins and lipids. Superoxide dismutase (SOD) is a major antioxidant scavenging enzyme it helps in removal of superoxide. Polymorphism of SOD2 gene may affect the scavenging effect of SOD enzyme which results in rise of oxidative stress in Type-II DM. The present study has been designed to study the effect of vitamin-C as add on therapy with antidiabetic drugs in type-2 diabetes mellitus patients associated with SOD2 gene polymorphism. A total of 64 type-II diabetes mellitus patients associated with SOD2 gene polymorphism (Ala16Val) were enrolled in present study and divided in to two groups i.e. Group A& B. There are three genotypes in each such as CC, CT& TT. Group-A& B patients were treated with metformin1000mg/day+ teneligliptin-20mg/day and metformin 1000mg/day+ teneligliptin 20mg/day+ vitamin C-1000mg/day respectively for 6 months. Glycemic control and oxidative stress was compared before and after 6 months of treatment in both groups. SPSS software was used to analyze the data. All the genotypes of both the groups had shown significant glycemic control (p<0.05). Significant reduction of TAC and elevation of MDA level was found in CT, TT genotype and CC, CT & TT genotype of group-A patients respectively (p<0.05). CC and CT genotype of group-B patients had shown significant elevation of TAC and reduction of MDA level as compared to baseline values (p<0.05). Good glycemic control and reduction of oxidative stress can be achieved with supplementation of vitamin-C along with antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk. [ABSTRACT FROM AUTHOR]

Objective: To investigate the preventive effects of a combined antioxidant drug (N‐acetylcysteine, vitamin E, and vitamin C [NEC]) on migraine outcomes. Migraine is characterized by increased oxidative stress and neurogenic inflammation in the brain; therefore, antioxidants may have a migraine preventive effect. Design: Randomized, double‐blind, sham‐controlled pilot study. Setting: Australian community. Subjects: Adults reporting 2 to 8 migraines per month for at least a year. Methods: After a 1‐month baseline period, 35 subjects completed 3 months of treatment with NEC (n = 19) or sham (n = 16) capsules. The primary outcome was the difference in mean number of headaches per month between baseline and final month of the trial for NEC and sham groups; secondary outcomes are listed below. Results: For NEC there was a significant decrease in mean number of headaches by 3.0 per month (P = 0.004) compared with 1.4 for sham (P = 0.073); there was no significant difference in these changes between the 2 groups (P = 0.052). Average monthly headache (P = 0.041) and migraine frequency (P = 0.018) were significantly less for NEC vs. sham. In NEC subjects, there was a significant decrease in average monthly migraine days (−3.1), moderate/severe headache days (−3.2), migraine duration, headache pain scores, and acute headache medication use. Conclusions: This is the first randomized controlled trial to find that combined antioxidant therapy with NEC reduces headaches and migraines in adult migraineurs. Given the limitations of this pilot study, an adequately powered randomized controlled trial is planned to further investigate antioxidant prophylaxis in migraine. [ABSTRACT FROM AUTHOR]

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI. [ABSTRACT FROM AUTHOR]

Dietary antioxidants are widely distributed in various types of our food. They are strongly associated with reduced risk of many chronic diseases such as atherosclerosis, cancer, and Alzheimer's diseases. They include vitamins such as vitamins A, E, C, and carotenoids. Also, some minerals like; zinc, manganese, copper, iron, and selenium are essential for the activity of antioxidant enzymes. Furthermore, dietary polyphenols and flavonoids are considered as potent antioxidant compounds. Vegetables, fruits, and edible herbs are the richest sources of such antioxidants. Antioxidants reduce oxidative stress, either directly by reducing reactive species or indirectly by enhancing the body antioxidant defense mechanisms in different ways. These may include upregulating gene expression of some antioxidant enzymes via a nuclear factor erythroid 2 related factor2 pathway. Administration of a mixture of antioxidants is beneficial since they act synergistically in various phases. The aims of this review are to summarize the different antioxidants from dietary sources and their role in the prevention of different diseases. [ABSTRACT FROM AUTHOR]

Study Design: A rat model of multifidus muscles injury and atrophy after posterior lumbar spine surgery.Objective: We determined the effect of ascorbic acid (AA) on the postoperative multifidus muscles in rat model.Summary Of Background Data: Previous studies show oxidative stress and inflammation are two main molecular mechanisms in multifidus muscle injury and atrophy after posterior lumbar surgery. AA may have a protective effect in postoperative multifidus muscles.Methods: Rats were divided into sham surgery, control surgery, and surgery plus AA groups. Multifidus muscles of the control and AA groups were excised from the osseous structures. The muscles were retracted continuously for 2 hours. In the sham and AA groups, AA was administered via oral gavage daily in the first week. In each group, the oxidative stress was evaluated by measuring malondialdehyde (MDA) and Total superoxide dismutase (T-SOD). The inflammation, fat degeneration, or fibrosis of multifidus muscle were evaluated by quantitative real-time polymerase chain reaction (q-PCR), histology, or immunohistochemical analysis.Results: T-SOD activity was significantly lower in the control group than that in the AA group in the first week. MDA levels were significantly higher in the AA group. Interleukin-6 and tumor necrosis factor-α in multifidus muscles also showed significant differences when treated with AA. The inflammation score on histology was significantly lower in the AA group postoperatively in the first week. In the long run, marker genes for fibrosis and fat degeneration, and fibrosis and fat degeneration scores, were significantly lower in the AA than the control group on days 14 and 28 postoperatively.Conclusion: In conclusion, AA attenuated the oxidative stress and inflammation response in the postoperative multifidus muscles, and remarkable differences were observed from the histological assessment and related marker genes expression. Our results provided important insight into the anti-inflammatory and anti-oxidative effects of AA in the postoperative multifidus muscles.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Abstract Structural and functional abnormalities in the cerebral microvasculature have been observed in Alzheimer's disease (AD) patients and animal models. One cause of hypoperfusion is the thickening of the cerebrovascular basement membrane (CVBM) due to increased collagen-IV deposition around capillaries. This study investigated whether these and other alterations in the cerebrovascular system associated with AD can be prevented by long-term dietary supplementation with the antioxidant ubiquinol (Ub) stabilized with Kaneka QH P30 powder containing ascorbic acid (ASC) in a mouse model of advanced AD (3 × Tg-AD mice, 12 months old). Animals were treated from prodromal stages of disease (3 months of age) with standard chow without or with Ub + ASC or ASC-containing vehicle and compared to wild-type (WT) mice. The number of β-amyloid (Aβ) plaques in the hippocampus and entorhinal cortex was higher in female than in male 3 × Tg-AD mice. Extensive regions of hypoxia were characterized by a higher plaque burden in females only. This was abolished by Ub + ASC and, to a lesser extent, by ASC treatment. Irrespective of Aβ burden, increased collagen-IV deposition in the CVBM was observed in both male and female 3 × Tg-AD mice relative to WT animals; this was also abrogated in Ub + ASC- and ASC-treated mice. The chronic inflammation in the hippocampus and oxidative stress in peripheral leukocytes of 3 × Tg-AD mice were likewise reversed by antioxidant treatment. These results provide strong evidence that long-term antioxidant treatment can mitigate plasma oxidative stress, amyloid burden, and hypoxia in the AD brain parenchyma. Highlights • 3 × Tg-AD mice show cerebrovascular basement membrane thickening in the hippocampus. • Female 3 × Tg-AD mice exhibit co-occurrence of hypoxia and high Aβ burden. • Chronic hippocampal inflammation is observed in 3 × Tg-AD mice. • Long-term antioxidant supplementation reduced neuropathological features of AD. • Antioxidants reduced peripheral leukocytes oxidative stress and neophobia. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the association of dietary total antioxidant capacity (TAC) with incidence of CKD in subjects with dysglycemia.Methods: We followed-up 1179 subjects aged ≥30 years with dysglycemia from the Tehran Lipid and Glucose Study (TLGS) for 3 years, who were initially free of CKD. Dietary intakes of TAC, vitamin C, vitamin E, and β-carotene were assessed by a food-frequency questionnaire at the baseline. Dietary TAC was estimated using the oxygen radical absorbance capacity method. Estimated glomerular filtration rate (eGFR) was calculated, using the Modification of Diet in Renal Disease Study equation and CKD was defined as eGFR <60 mL/min/1.73 m2. Odds ratios (ORs) using multivariable logistic regression were reported for the association of incident CKD with dietary TAC.Results: A total of 197 (16.7%) cases of incident CKD were recorded after 3 years of follow-up. After adjustment for age, sex, smoking, physical activity, body mass index, hypertension, and total energy intake, the top tertile of dietary TAC compared to the bottom was associated with 39% [95% confidence interval (CI) = 0.40-0.93] lower risk of incident CKD (P for trend = 0.025). Furthermore, the highest tertile of vitamin C intake compared to the lowest risk of incident CKD was decreased (OR 0.60; 95% CI 0.38-0.93, P trend 0.023). Intakes of vitamin E and β-carotene were not significantly associated with incident CKD risk.Conclusion: Our findings suggest that diets high in TAC are associated with a lower risk of incident CKD among subjects with hyperglycemia after 3 years of follow-up. [ABSTRACT FROM AUTHOR]

Excessive use of organophosphate insecticides, including fenitrothion (FNT) can cause detrimental consequences in non-target organisms. Selenium (Se) and vitamin C (Vit C) possess protective abilities against various toxic compounds due to their antioxidative properties. Accordingly, the aim of the present study was to examine the possible ameliorative effects of Se and Vit C in hepatotoxicity induced by FNT. For the purpose of this study, male Wistar albino rats were divided into control and groups treated with Se (0.5 mg/kg b.w, as Na 2 SeO 3 ) and Vit C (100 mg/kg b.w), FNT (20 mg/kg b.w) and FNT in cotreatment with Se and Vit C for 30 days. The current data showed a reduction in absolute and relative liver weight after FNT administration. Increased activities of liver enzymes (AST, ALT, ALP, LDH and GGT) indicated liver damage. FNT alone caused significant alterations in biochemical parameters (glucose and total bilirubin). Elevation in LPO level along with decreased activities of antioxidant enzymes (SOD, CAT, GSH-Px) and GSH content reflected the presence of oxidative stress. Coadministration of FNT with Se and Vit C exhibited hepatoprotective role confirmed by reduction of oxidative stress levels and restoration in the values of examined parameters. Because of their beneficial effects, Se and Vit C may be used in reducing injuries caused by pesticides. [ABSTRACT FROM AUTHOR]

Highlights • DEHP induced BTB integrity disruption through activating p38 MAPK signaling pathway. • In the process of DEHP induced BTB integrity impairment, oxidative stress is the initiating factor. • Antioxidants—vitamin E and C can rescue BTB integrity disruption induced by DEHP. Abstract As an environmental endocrine disruptor, Di-(2-ethylhexyl) phthalate (DEHP) affects blood-testis barrier (BTB)-associated proteins expression, which compromises BTB integrity and causes infertility. Notably, DEHP-induced testicular toxicity is related to oxidative stress, but the specific mechanism remains unclear. Therefore, we sought to investigate this mechanism and determine whether vitamin C and vitamin E administration would attenuate the BTB impairment induced by DEHP in vivo and by Mono-(2-Ethylhexyl) Phthalate (MEHP) in vitro, respectively. HE staining and EM found that DEHP exposure led to spermatogenesis dysfunction and BTB disruption, respectively. The Western blot and immunofluorescence results showed that DEHP exposure caused BTB impairment through oxidative stress-mediated p38 mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, Vitamin E and vitamin C could alleviate the oxidative stress, block DEHP-induced spermatogenesis dysfunction and BTB disruption by inhibiting p38 MAPK signaling pathway. In summary, vitamin E and vitamin C are good candidates for the treatment of DEHP-induced male infertility. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of applied continuous 2.45 GHz electromagnetic radiation (EMR), which might cause physiopathological or morphological changes in the ovarian, fallopian tubal, and uterine tissues of rats. We proposed that the addition of vitamin C (Vit C) may reduce these severe effects. Eighteen female Sprague Dawley rats were randomly divided into three groups with six animals in each: Sham, EMR (EMR, 1 h/day for 30 days), and EMR + Vit C (EMR, 1 h/day for 30 days 250 mg/kg/daily). Total oxidant status (TOS) and oxidative stress index (OSI) levels increased (p = 0.011 and p = 0.002, respectively) in the EMR-only group in ovarian tissues. In all tissues, TOS and OSI levels significantly decreased in the Vit C-treated group in ovarian, fallopian tubal, and uterine tissues (p < 0.05). Anti-müllerian hormone levels significantly increased in the EMR group (p < 0.05) and decreased in the Vit C-treated groups. Estrogen (E2) levels were unchanged in the EMR group, as the differences were not statistically significant. Immunohistochemical examination of the ovaries revealed significant increases in Caspase-3 expressions in the epithelial cells of the EMR group (p < 0.05). In the EMR group, hyperemia was observed in uterine tissues. Also, Caspase-3 and Caspase-8 were significantly increased in the EMR group (p < 0.001). Caspase-3 was significantly diminished with Vit C application in the ovarian and uterine tissues (p < 0.05). Caspase-8 was significantly diminished only in uterine tissues (p < 0.05). These results indicate that prolonged EMR exposure induced physiopathological changes in the ovarian, fallopian tubal, and uterine tissues due to oxidative damage. Under the conditions of this study, Vit C may have protective effects on female reproductive system against oxidative damage. [ABSTRACT FROM AUTHOR]

Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100 mg/kg/day, 6 days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6 days a week for 4 weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short- and long-term memory (p < .05). On the other hand, VitC protected memory impairment induced by WTS (p < .05). Moreover, VitC prevented the reduction in hippocampus ratio of GSH/GSSG (p < .05) induced by WTS. Furthermore, WTS reduced hippocampus activity of glutathione peroxidase (GPx) and catalase, which were also normalized by VitC treatment. However, thiobarbituric acid reactive substance (TBARS) levels were not changed by WTS and/or by VitC (p > .05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure. [ABSTRACT FROM AUTHOR]

Background Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity. Methods Human umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of 14 C-inulin. Viability was measured by trypan blue exclusion. Intracellular ascorbate was measured by HPLC. Results CFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability. Conclusions CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis. [ABSTRACT FROM AUTHOR]

In this review, we summarize the involvement of ascorbic acid in neurodegenerative diseases by presenting available evidence on the behavioral and biochemical effects of this compound in animal models of neurodegeneration as well as the use of ascorbic acid as a therapeutic approach to alleviate neurodegenerative progression in clinical studies. Ascorbate, a reduced form of vitamin C, has gained interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. In the brain, ascorbate exerts neuromodulatory functions and scavenges reactive oxygen species generated during synaptic activity and neuronal metabolism. These are important properties as redox imbalance and abnormal protein aggregation constitute central mechanisms implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Indeed, several studies have indicated an association between low serum ascorbate concentrations and neurodegeneration. Moreover, ascorbic acid is a suitable candidate for supplying either antioxidant defense or modulation of neuronal and astrocytic metabolism under neurodegenerative conditions. Ascorbic acid acts mainly by decreasing oxidative stress and reducing the formation of protein aggregates, which may contribute to the reduction of cognitive and/or motor impairments observed in neurodegenerative processes. Although several studies support a possible role of ascorbic acid administration against neurodegeneration, more researches are essential to substantiate the existing results and accelerate the knowledge in this field. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is elevated in very early stages of Alzheimer’s disease and exacerbates oxidative stress, which contributes to disease pathology. Mitochondria were isolated from 4-month-old wild-type mice, transgenic mice carrying the APP SWE and PSEN1 dE9 mutations, mice with decreased brain and mitochondrial ascorbate (vitamin C) via heterozygous knockout of the sodium dependent vitamin C transporter (SVCT2 +/- ) and transgenic APP/PSEN1 mice with heterozygous SVCT2 expression. Mitochondrial isolates from SVCT2 +/- mice were observed to consume less oxygen using high-resolution respirometry, and also exhibited decreased mitochondrial membrane potential compared to wild type isolates. Conversely, isolates from young (4 months) APP/PSEN1 mice consumed more oxygen, and exhibited an increase in mitochondrial membrane potential, but had a significantly lower ATP/ADP ratio compared to wild type isolates. Greater levels of reactive oxygen species were also produced in mitochondria isolated from both APP/PSEN1 and SVCT2 +/- mice compared to wild type isolates. Acute administration of ascorbate to mitochondria isolated from wild-type mice increased oxygen consumption compared with untreated mitochondria suggesting ascorbate may support energy production. This study suggests that both presence of amyloid and ascorbate deficiency can contribute to mitochondrial dysfunction, even at an early, prodromal stage of Alzheimer’s disease, although occurring via different pathways. Ascorbate may, therefore, provide a useful preventative strategy against neurodegenerative disease, particularly in populations most at risk for Alzheimer’s disease in which stores are often depleted through mitochondrial dysfunction and elevated oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Phenylhydrazine (PHZ) as a strong oxidant agent causes variety of toxic effects including alterations in the biochemical and cardiac tissue. The aim of the present study was to investigate the effects of royal jelly (RJ) and vitamin C (vit C) against PHZ-induced cardiotoxicity in mice. Materials and Methods: Adult male mice were randomly assigned to eight groups of eight mice each. PHZ was administered to four groups of mice at a dose of 60 mg/kg per 48 hours intraperitoneally for 35 days. Three of these groups received vit C (250 mg/kg per day) intraperitoneally, RJ (100 mg/kg per day) orally and vit C+RJ with same doses four hours before PHZ administration, respectively. A vehicle-treated control group and vit C, RJ and vit C+RJ control groups were also included. Results: RJ and vit C significantly decreased (p< 0.05) the serum level of malondialdehyde and creatine kinase (CK-BM) that had been increased by PHZ. Also, RJ and vit C increased the total antioxidant capacity and supraxoid dismutase serum that had been decreased by induced PHZ. Moreover, RJ and vit C could improve the tissue damages induced by PHZ such as diffused edema, hemorrhage, congestion, hyaline exudates, necrosis and also fibrosis tissue in heart tissue. Conclusion: It seems that Vit C and RJ can minimize PHZ-induced cardiotoxicity in mouse through oxidative reactions inhibition. [ABSTRACT FROM AUTHOR]

Background: Diabetic gastroparesis is a common complication of diabetes mellitus, which mainly affects women. Previous studies have demonstrated that oxidative stress is involved in its onset and development.Aims: This study evaluated the role of vitamin C on diabetes-associated gastric dysmotility.Methods: Female rats with streptozotocin-induced diabetes were treated with vehicle (water, 1 mL/kg, p.o.), vitamin C (300 mg/kg/day, p.o.), or insulin (6 IU/day, s.c.). Gastric emptying, in vitro gastric contractility, and biochemistry parameters were analyzed at the end of the treatment (i.e. 8 weeks after the diabetes induction).Results: Vitamin C reversed the delayed gastric emptying of diabetic rats to normal levels, and avoided the changes in the contractile responses to acetylcholine (0.1 nM-1 µM), but not to 5-hydroxytryptamine (0.1 nM-1 µM), in the pylorus and fundus from diabetic rats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabetic rats treated with vitamin C. Notably, the vitamin C reestablished the reduced glutathione levels by 77% and decreased the reactive oxygen species content by 60% in the gastric tissue from diabetic rats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabetic rats. Unsurprisingly, insulin treatment normalized all parameters evaluated.Conclusions: Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabetic rats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus. [ABSTRACT FROM AUTHOR]

We previously reported that Vitamin C (Vit C) protects against doxorubicin (Dox)-induced cardiotoxicity by reducing oxidative stress, p38 mitogen-activated kinase (MAPK) and p53 activation and rescuing cell death in isolated adult cardiomyocytes. The pattern of activation and the role of oxidative stress as well as down-stream mechanisms for such protection remain elusive. Therefore the present study aims to analyze time-dependant generation of reactive oxygen species (ROS) and the activation of stress induced signalling pathways in cardiomyocytes treated with Dox and Vit C. The data provides further understanding of heart pathophysiology in response to Dox at the cellular level, and may help to optimize the timing of various therapeutic approaches. Cardiomyocytes isolated from adult Sprague-Dawley rats were exposed to Dox (10 μM), Vit C (25 μM), and Dox + Vit C for different time intervals up to 24 h. p38-JNK (SB203580) and p53 (pifithrin-α) inhibitors were used to determine the role of each respective signalling protein. Dox administration to cardiomyocytes increased the levels of ROS in a time-dependent manner that followed the activation of stress-induced proteins p53, p38 and JNK MAPKs, culminating in an increase in autophagy and apoptosis markers. Dox-induced increase in ROS was alleviated by Vit C adjuvant treatment at all time-points and this was also correlated with blunting of the activation of the studied signaling pathways leading to the prevention of apoptosis and preservation of cell viability. Protective effect of Vit C against the activation of stress induced proteins, autophagy and apoptosis was mainly attributed to its antioxidant properties even though blockage of p38, JNK and p53 by pharmacological inhibitors also suppressed Dox-induced apoptosis. ROS is defined as a key inducer of cardiomyocyte damage under Dox exposure; Vit C could effectively counteract all Dox-induced changes in cardiomyocytes and may potentially be used as an antioxidant adjuvant therapy to protect against Dox-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Herbal drugs play a crucial function to protect organisms from the toxic effect of some compounds. The present study was designed to evaluate the protective effects of Teucrium Polium (TP) aqueous extract and vitamin C (Vit C) against carbon tetrachloride (CCl 4 ) which induced toxicity in rats. Male albino Wistar rats were divided into six groups: group I was used as controls, group II received CCl 4 in olive oil (0.5 ml/kg) by gavage, and group III received CCl 4 in olive oil (0.5 ml/kg) by gavage after three days of receiving TP (5 g/l), orally, for seven days; Group IV received TP (5 g/l) alone, orally, for seven days, Group V received CCl 4 in olive oil (0.5 ml/kg) by gavage after three days of receiving Vit C (250 mg/kg) by intramuscular injection and Group VI received Vit C (250 mg/kg) alone by intramuscular injection, for day seven. Some biochemical and hematological parameters were investigated. Our results showed that the administration of CCl 4 caused hepatotoxicity as monitored by the significant increase in the levels of hepatic markers enzymes (lactate dehydrogenase (LDH), Alkaline phosphatase (PAL), total bilirubin (TB) and Gamma glutamyl transferase (γGT) levels) and a decrease in hematological parameters such as white blood cell (WBC), red blood cell count (RBC), mean corpuscular hemoglobin concentration (MCHC) and blood platelet count (PLT). Treatment with TP or Vit C appeared to be effective against hematotoxic and the liver changes induced by CCl 4 , as evidenced by the improvement of the parameters cited above. The CCl 4 -treated group demonstrated a significant increase of malondialdehyde (MDA) levels in erythrocytes thus causing a reduction in antioxidant defense system. Pretreatment with TP or Vit C improved the biochemical analyses, hematological parameters, and antioxidant defense system. [ABSTRACT FROM AUTHOR]

Ferrous iron can be converted to ferric iron by oxidative stress which results in the formation of methemoglobin. Consequently, the oxygen dissociation curve is shifted to the left, which leads to tissue hypoxia and ultimately may cause death. Acquired methemoglobinemia can be due to a host of offending agents and chemicals including nitrites, local anesthetics, aniline and antimalarial drugs. There are several approaches to the management of methemoglobinemia. The first step is to stop the offending agent and initiate supportive measures. Methylene blue can be used successfully provided the patient has no evidence of glucose 6 phosphate deficiency. Hyperbaric oxygen and intravenous ascorbic acid are other treatment options. We present a case of unusually severe methemoglobinemia (82% methemoglobin) secondary to occupational exposure that failed to respond to several lines of management including methylene blue, red cell exchange, intravenous ascorbic acid, and hyperbaric oxygen. However, the patient responded swiftly to plasmapheresis started upon suspicion of concomitant thrombotic thrombocytopenic purpura, and he subsequently recovered completely. Thus, plasmapheresis may have a role in severe methemoglonbinemia unresponsive to standard treatment options. [ABSTRACT FROM AUTHOR]

Introduction: Dazinon (DZN) as organophosphate insecticide induces oxidative stress. Vitamins E and C are antioxidants protecting cells from oxidative stress. Objective: To determine the modulation of diazinon-induced oxidative stress by vitamins E and C in rat brain. Materials and Methods: In present experimental study, male Wistar rats were randomly divided into six groups including: control (corn oil as DZN solvent), DZN (100 mg/kg), vitamin E (150 mg/kg), vitamin C (200 mg/kg), vitamin E+DZN and vitamin C+DZN groups, all of which were given intraperitoneally. 24 hours after injection, animals were anesthetized by ether, and brain tissue was quickly removed. After tissues hemogenation, superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and lactate dehydrogenase (LDH) activities, as well as glutathione (GSH) and malondialdehyde (MDA) levels were determined by biochemical methods. Results: DZN increased SOD (p<0.001) and GST (p<0.01) activities and MDA level (p<0.01), while it decreased CAT and LDH activities and GSH content (p<0.01) in brain compared with the control group. Administration of vitamin E or vitamin C inhibited the changed in these parameters. Discussion: Administration of vitamin E or vitamin C as antioxidant decreases DZN toxicity by scavenging free radicals but it does not protect completely. [ABSTRACT FROM AUTHOR]

Background/aims: The main purpose of the present study was to investigate the effects of vitamin C and E supplements on the antioxidant capacity of erythrocytes obtained from young and aged rats.Methods: Male Wistar rats aged 3 and 24 months were used. Vitamins C and E were injected at doses of 200 mg/kg (day) intraperitoneally in young and aged groups. The antioxidant capacity, oxidant stress parameters, and deformability of red blood cells collected from different age stages were evaluated. An in vitro oxidation system was constructed to explore the mechanisms of antioxidant capacity change in the vitamin treatment groups.Results: Treatment with vitamins C and E can effectively restore the antioxidant capacity and deformability of red blood cells (RBCs) in aged rats. Under in vitro oxidative conditions, an age-dependent decline in the influx rate of L-cysteine was observed. This was significantly improved following treatment with vitamins C and E.Conclusion: We present evidence of an improvement in the antioxidant capacity of RBCs by treatment with vitamins C and E in aged rats. These observations also suggest that treatment with vitamins C and E improves glutathione synthesis by enhancing the influx rate of L-cysteine through the modification of membrane proteins and lipids. [ABSTRACT FROM AUTHOR]

What is known and objective: Hexavalent (VI) chromium is a powerful oxidant that can produce cellular oxidative stress and multi‐organ system dysfunction. The role of antioxidants such as N‐acetylcysteine (NAC) and ascorbic acid in alleviating organ damage in humans remains unclear. Case description: We present a 47‐year‐old male who ingested 30 mL of plating solution and developed hepatic injury. He was treated with NAC and ascorbic acid with improvement in hepatic function. However, his clinical conditions and jaundice worsened again after discontinuing these therapies. What is new and conclusion: Our findings suggest a potential role for antioxidant therapy for acute hexavalent chromium poisoning. [ABSTRACT FROM AUTHOR]

In this study, biochemical changes and histological structure of rat liver after bendiocarb administration and possible preventive effects of vitamins C and E were studied. The animals were given with bendiocarb, vitamin C and vitamin E, daily 0,8 mg/kg of body weight (bw), 100 mg/kg-bw and 100 mg/kg-bw for 28 days, respectively. Lipid peroxidation, antioxidant enzyme activities, histological alterations and antioxidant capacity assays of liver and also liver function tests and lipid profile were measured. Bendiocarb treatment decreased the antioxidant enzyme activities, FRAP and TEAC values and increased malondialdehyde levels compared to control. Also, there were statistically significant alterations in liver function tests, lipid profile parameters and histopathological changes in bendiocarb treated groups. Vitamins C and E showed protective effects against examining parameters. According to results we can say that co-treatment of vitamin C and vitamin E may be more effective than use of them alone. [ABSTRACT FROM AUTHOR]

Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health status. A popular topic of discussion in medical research is the potential association between oxidative stress and negative outcomes. Systemic biomarkers that represent oxidative stress can be found in saliva. It is unclear, however, if saliva is an accurate biospecimen as is blood and/or plasma. Exercise can induce oxidative stress, resulting in a trend of antioxidant supplementation to combat its assumed detriments. Vitamin C is a popular antioxidant supplement in the realm of sports and exercise. One potential avenue for evaluating exercise induced oxidative stress is through assessment of biomarkers like vitamin C and malondialdehyde in saliva. At present, limited research has been done in this area. The current state of research involving exercise-induced oxidative stress, salivary biomarkers, and vitamin C supplementation is reviewed in this article. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to evaluate the probable protective effect of vitamin C and vitamin E on diclofenac-induced acute nephrotoxicity using biochemical, molecular and histopathological examination in rats following administration of diclofenac sodium (50 mg/kg, I.M). Methods Ninety male Wister rats were allotted in six equal groups. Rats in the 1st group (control group) were injected with physiological saline, while rats in the 2nd group (C-group) were given vitamin C (100 mg/kg orally via stomach tube) for 5 successive days. The 3rd group (E-group) was given vitamin E (250 mg/kg orally in diet) for 5 successive days. Rats in the 4th group (D-group) were injected by diclofenac sodium (50 mg/kg, I.M) for 5 successive days. The 5th group (DvC-group) was given diclofenac sodium (50 mg/kg, I.M) and vitamin C (100 mg/kg orally via stomach tube) for 5 successive days. Rats in the 6th group (DvE-group) were given diclofenac sodium (50 mg/kg, I.M) and vitamin E (250 mg/kg orally in diet) for 5 successive days. Blood samples were collected two days post treatment (1st week of experiment), 2nd and 4th week of the experiment for assessment of urea, creatinine, malondialdehyde, nitric oxide and superoxide dismutase activities. At the end of 4th week, rats were sacrificed and kidneys were excised for biochemical analyses, histopathological evaluation and determination of kidney interleukin-1β, interleukin-18, demsin and nepherin expressions in by reverse transcriptase–polymerase chain reaction (RT-PCR). Results The results showed that, diclofenac induced severe kidney damage as indicated by histopathological changes and increased serum oxidative stress parameters. Behavioral changes were monitored; a significant increase in uremia in intoxicated animals was also noted indicating that diclofenac sodium provoked kidney damage in rats. Application of vitamin C (DvC-group) and vitamin E (DvE-group) were found to improve the abovementioned abnormalities. Conclusion The present data suggest that, vitamin C and vitamin E might play an important role in reducing oxidative stress and kidney damage induced by diclofenac sodium. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP)-induced nephrotoxicity is mediated via oxidative stress and may be alleviated using antioxidant activity. Although megadose of vitamin C may cause oxalate nephropathy and apoptosis, the antioxidant effect of vitamin C may be beneficial when given along with CDDP. The objective of this study was to investigate the renoprotective effects of megadose vitamin C on rats receiving CDDP. Rats were divided into 4 groups: group 1, control rats (CONT); group 2, vitamin C-treated rats (VIT C); group 3, CDDP-treated rats (CDDP) and group 4, CDDP + vitamin C-treated rats (CDDP + VIT C). Vitamin C (1000 mg/kg) was given intravenously to the VIT C and CDDP + VIT C groups while CDDP (6 mg/kg) was injected intraperitoneally into the CDDP and CDDP + VIT C groups. Renal function, oxidative stress, apoptosis and histopathology were investigated. At 5 days after injection, CDDP caused renal impairment as shown by significant increases in plasma concentrations of creatinine (PCr), urea nitrogen (PUN), urinary excretion of electrolytes (Na+, K+ and Cl-) and protein (P<0.05). Plasma malondialdehyde (P-MDA) and urinary MDA and creatinine ratio (U-MDA/Cr) were also increased (P<0.05). Kidney PCR products of antiapoptosis/proapoptosis (Bcl-2/Bax) were reduced by CDDP while histopathologic results showed severe massive tubular necrosis. Giving megadose vitamin C along with CDDP showed improvement on all renal function parameters and oxidative stress parameters except proteinuria. The vitamin C caused improvement on tubular cell lesions, but did not alter the Bcl-2/Bax level. It is concluded that megadose vitamin C can provide protection against CDDP-induced kidney injury by antioxidant activity. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in the pathophysiology of many reproductive complications including infertility, miscarriage, pre-eclampsia, fetal growth restriction and preterm labour. The presence of excess reactive oxygen species can lead to cellular damage of deoxyribonucleic acids, lipids and proteins. Antioxidants protect cells from peroxidation reactions, limiting cellular damage and helping to maintain cellular membrane integrity. There is overwhelming evidence for oxidative stress causing harm in reproduction. However, there is sparse evidence that supplementation with commonly used antioxidants (mostly vitamins C and E) makes any difference in overcoming oxidative stress or reversing disease processes. There may be potential for antioxidant therapy to ameliorate or prevent disease, but this requires a thorough understanding of the mechanism of action and specificity of currently used antioxidants. [ABSTRACT FROM AUTHOR]

The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days. Control group was treated with excipient. Previous tests selected the doses of juglone and Q7 plus ascorbate (1 and 100 mg/kg, respectively). Samples of ascitic fluid were collected to evaluate carbonyl proteins, GSH and activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Hypoxia inducible factor HIF-1α, GLUT1, proteins driving cell cycle (p53, p16 and cyclin A) and apoptosis (poly-ADP-polymerase PARP, Bax and Bcl-xL) were assessed by western blot. Tumor cells were categorized by the phase of cell cycle using flow cytometry and type of cell death using acridine orange/ethidium bromide. A glucose uptake assessment was performed by liquid scintillation using Ehrlich tumor cells cultured with 14 C-deoxyglucose. Treatments caused increased protein carbonylation and activity of antioxidant enzymes and decreased levels of GSH, HIF-1α, GLUT1 and glucose uptake in tumor cells. They also caused increased number of tumor cells in G1, p53 and p16 activation and decreased cyclin A, but only when combined with ascorbate. Apoptosis was induced mostly when treatments were done with ascorbate, causing PARP and Bax cleavage, and increased Bax/Bcl-xL ratio. Juglone and Q7 in combination with ascorbate caused inhibition of tumor progress in vivo by triggering apoptosis and cell cycle arrest associated with oxidative stress, suppression of HIF-1 and uncoupling of glycolytic metabolism. [ABSTRACT FROM AUTHOR]

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Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxidonitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)- L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. [ABSTRACT FROM AUTHOR]

Sodium vitamin C transporter 2 (SVCT2) plays a key role in transporting ascorbic acid (AA), an important intracellular antioxidant, into neurons. It is well known that ethanol (EtOH) abuse causes significant neurodegeneration, as well as endogenous AA release in certain encephalic regions. Here, we identified that SVCT2 forms part of a self-defense mechanism that protects against oxidative stress in binge drinking rats, and SVCT2 levels are correlated with antioxidants and neuronal injury. Four days of binge drinking led to massive neuron degeneration in prefrontal cortex (PFC), accompanied by increased levels of 4-hydroxynonenal (4-HNE)-adducted proteins and SVCT2 expression, as well as dramatic changes in AA levels in rat brain. AA levels were decreased in PFC and increased in cerebrospinal fluid (CSF) after binge drinking, but returned to normal on the 7th day following EtOH withdrawal. These processes were further evaluated in primary cortical neurons exposed to 100 mM EtOH in vitro . Neurons transfected with SVCT2 siRNA were more susceptible than controls to certain aspects of EtOH-induced injury, including cell death, dendrite damage and increased oxidative stress. EtOH-induced up-regulation of SVCT2 was associated with activation of JNK and p38 MAPKs and the NF-κB pathway. More importantly, miRNA-125a-5p was down-regulated in PFC of 4-day binge drinking rats and negatively regulated protein expression during EtOH-induced neuronal injury. MiR-125a-5p over-expression attenuated intracellular AA levels, promoted cell death and suppressed the EtOH-induced up-regulation of p38 MAPK and SVCT2, which suggested that miR-125a-5p plays an important role in SVCT2 function in EtOH-induced neuronal injury. We speculate that SVCT2, possibly regulated by JNK/p38 MAPKs, NF-κB signaling and miR-125a-5p, has a neuroprotective effect against EtOH-induced oxidative stress. Promotion of SVCT2 expression or stimulation of SVCT2 activity may be a promising therapeutic strategy for the prevention of EtOH-associated neurodegeneration. [ABSTRACT FROM AUTHOR]

Context: Oxidative stress plays a key role in the patho-physiology of hypertension. (−)-Epicatechin has many important biological properties.Objective: The present study was undertaken to evaluate effect of (−)-epicatechin on protein carbonyl content in gender-based hypertensive patients and normal subjects.Methods: The study was carried out on 83 normal (male: 42; female: 41) and 62 hypertensive subjects (male: 32; female: 30).In vitroeffect on (−)-epicatechin and L-ascorbic acid was estimated on protein carbonyl content.Results: Result showed a significant (p < 0.001) increase in protein carbonyl content in hypertensive patients but no gender-based difference was observed. (−)-epicatechin shows significant (p < 0.001) dose-dependent effect as compared to L-ascorbic acid, which is manifested as decrease in protein carbonyl content.Conclusion: We hypothesizes that a higher intake of (−)-epicatechin may provide protection against hypertension in males and females. [ABSTRACT FROM AUTHOR]

Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150 mg/kg, gavage) or vehicle (distilled water, gavage) 1 h before FA exposure (0.92 mg/m 3 , 1 h/day, 5 days/week), for 21 days, and the 30 days old offspring were submitted to LPS injection ( Salmonella abortus equi , 5 mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a major health problem worldwide with urgent need for new and effective anti-cancer approaches that allow treating, increasing survival and improving life quality of patients. At pharmacological concentrations, ascorbic acid (AA) exerts a selective cytotoxic effect, whose mechanism of cytotoxicity remains unsolved. It has been suggested that it depends on the production of extracellular hydrogen peroxide, using ascorbate radical as an intermediate. The aim of this study was to evaluate the effects induced by AA in three colon cancer cell lines, as well as, possible cell death mechanisms involved. Our results showed that pharmacological concentrations of AA induce anti-proliferative, cytotoxic and genotoxic effects on three colon cancer cell lines under study. We also found that AA can induce cell death by an increment of oxidative stress, but also mediating a ROS-independent mechanism, as observed in LS1034 cells. This work explores AA anti-tumoral effects and highlights its applicability in the treatment of CC, underlying the importance of proceeding to clinical trials. [ABSTRACT FROM AUTHOR]

Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-ĸB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema. [ABSTRACT FROM AUTHOR]

The impact of ascorbate on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. Heatstroke is defined as a form of excessive hyperthermia associated with a systemic inflammatory response that results in multiple organ dysfunctions in which central nervous system disorders such as delirium, convulsions, and coma are predominant. The thermoregulatory, immune, coagulation and tissue injury responses of heatstroke closely resemble those observed during sepsis and are likely mediated by similar cellular mechanisms. This study was performed by using the characteristic high lethality rate and sepsis-mimic systemic inflammatory response of a murine model of heat stroke to test our hypothesis that supra-physiological doses of ascorbate may have therapeutic use in critical care. We demonstrated that parenteral administration of ascorbate abrogated the lethality and thermoregulatory dysfunction in murine model of heat stroke by attenuating heat stroke-induced accelerated systemic inflammatory, coagulation responses and the resultant multiple organ injury, especially in hypothalamus. Overall, our findings support the hypothesis and notion that supra-physiological doses of ascorbate may have therapeutic use in critical care. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans.Methods: We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration.Results: Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans.Conclusions: The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration. [ABSTRACT FROM AUTHOR]

Aim: In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae.Methods: The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood.Results: Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation.Conclusion: The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation. [ABSTRACT FROM AUTHOR]

The present study evaluated the synergistic effects of the association of ascorbic acid and α-tocopherol on myenteric in the jejunum of diabetic rats. The rats were randomly divided into four equal groups: untreated normoglycemic (UC), untreated diabetic (UD), ascorbic acid and α-tocopherol-treated normoglycemic (CAE) and ascorbic acid and α-tocopherol-treated diabetic (DAE). The rats from the CAE and DAE group received supplementation with ascorbic acid (1 g/L in water) and α-tocopherol (1% in chow). At 210-days-old, the animals were sacrified and their jejunum was collected and submitted to immunohistochemistry. Quantitative and/or morphometric analysis were performed. Supplementation with ascorbic acid and α-tocopherol prevented the cell loss of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We also observed a reduction of the CGRP nerve fiber varicosities and the prevention of the increased cell body size of submucosal VIP neurons ( p < 0.05). The association of ascorbic acid and α-tocopherol reduced the deleterious effects of diabetes promoting protection on the enteric neurons. [ABSTRACT FROM AUTHOR]

This study examined the effect of an antioxidant intervention in biomarkers of inflammation and oxidative stress (OS) in the blood of Down syndrome (DS) children and teenagers during four different stages. A control group was composed by healthy children (n=18), assessed once, and a Down group composed by DS patients (n=21) assessed at the basal period (t0), as well as after 6 months of antioxidant supplementation (t1), after 12 months (after interruption of the antioxidant intervention for 6 months) (t2), and again after further 6 months of antioxidant supplementation (t3). Biomarkers of inflammation (myeloperoxidase activity - MPO and levels of IL-1β and TNF-α) and OS (thiobarbituric acid reactive substances - TBARS, protein carbonyls - PC), reduced glutathione (GSH), uric acid (UA) and vitamin E levels, as well as antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and gamma-glutamyltransferase (GGT) activities, were measured after each period. After the antioxidant supplementation, the activities of SOD, CAT, GPx, GR, GGT and MPO were downregulated, while TBARS contents were strongly decreased, the contents of GSH and vitamin E were significantly increased, and no changes in G6PD and GST activity as well as in UA and PC levels were detected. After the interruption of the antioxidant therapy for 6 months, DS patients showed elevated GPx and GGT activities and also elevated UA and TBARS levels. No changes in SOD, CAT, GR, GST, G6PD and MPO activities as well as in GSH, vitamin E, PC, TNF-α and IL-1β levels were detected. The results showed that the antioxidant intervention persistently attenuated the systemic oxidative damage in DS patients even after a relatively long period of cessation of the antioxidant intervention. [ABSTRACT FROM AUTHOR]