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Introduction: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice. Methods: The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate. Results: A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment. Discussion: Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions. Conclusions: l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst. [ABSTRACT FROM AUTHOR]

Diabetes is often associated with increased oxidative stress caused by an imbalance between detoxification and ROS production. Unfortunately, many commercial drugs available today for treating this disease have adverse side effects and ultimately fail to restore glucose homeostasis. Therefore, finding a dietary anti-diabetic remedy that is safe, effective, and economical is crucial. In this study, GC–MS analysis, subsequent HPLC-assisted fractionation, and SPE-based purification led to identifying and purifying of key components such as phloroglucinol and total procyanidin dimer (procyanidin dimer and procyanidin dimer gallate) from methanolic seed extract of Vitis vinifera. In-vitro anti-diabetic screening of various fractions derived from methanolic extract along with individual components and their combinations revealed the potential synergistic behaviour of phloroglucinol and total procyanidin dimer with the lowest IC50 of 48.21 ± 3.54 µg/mL for α-glucosidase and 63.06 ± 5.38 µg/mL for α-amylase inhibition which is found to be superior to the effect shown by the standard Epigallocatechin gallate. Later Glucose utilization studies demonstrated the concentration-dependent effect of Phloroglucinol and total procyanidin dimer, and that has raised the glucose uptake by approximately 36–57% in HepG2 cells and 35–58% in L6 myocytes over a concentration of 50–100 µg/mL. The superior anti-diabetic effect of Phloroglucinol and total procyanidin dimer was proved by the suppression of oxidative stress with an IC50 of 7.92 ± 0.36 µg/mL for DPPH scavenging and 16.87 ± 1.24 µg/mL for SOD scavenging which is competent with the standard ascorbic acid. According to this study, suppressing ROS levels by phloroglucinol and total procyanidin dimer would be the underlying mechanism for the synergistic anti-diabetic effect of this combination. [ABSTRACT FROM AUTHOR]

Excessive dietary fat is mainly responsible for metabolic diseases including atherosclerosis and cardiovascular disease. We have evaluated the role of Vitamin C in an experimental hyperlipidemic model of rats (male Wistar rat 12–16 months). The hyperlipidemic model of the rat was created by treatment with an atherogenic suspension: cholesterol, cholic acid, and coconut oil, for 30 days once daily, and supplemented with Vitamin C (Ascorbic acid) doses of 0.5 g/kg body weight (orally) for the 30 days once daily. Bodyweight, fasting glucose, triglyceride, cholesterol, ROS (Reactive oxygen species), MDA (Malondialdehyde), FRAP (Ferric reducing the ability of plasma), GSH (Reduced glutathione), PCO (Protein carbonyl), PON-1(Paraoxonase-1), AGE (Advanced glycation end product), PMRS (Plasma membrane reduced system), and inflammatory cytokines (TNF-α and IL-6) were estimated in blood and plasma. Our result shows that oxidative stress, and inflammatory markers, were increased in the HFD-treated group of rats. Vitamin C supplementation protected against lipidemic and, oxidative stress. We conclude that Vitamin C may be useful in maintaining cellular redox balance and protecting against lipidemic stress. [ABSTRACT FROM AUTHOR]

Objectives: Oxidative stress level takes part in the development of cognitive decline. However, the association between total antioxidant capacity (TAC) from diet and cognitive function is controversial. The aim of this study was to investigate the relationship between TAC and the cognitive function of older adults in the U.S. Design: A cross-sectional study. Setting: National Health and Nutrition Examination Surveys database. Participants: 2712 older adults aged over 60 years. Measurements: TAC was calculated from 8 antioxidative vitamins based on the reference values for vitamin C equivalent antioxidant capacity obtained from individuals' 24 h dietary recall. Four memory-related assessments were employed [Immediate Recall test (IRT), Delayed Recall test (DRT), Animal Fluency test (AFT), and Digit Symbol Substitution test (DSST)]. Results: Among the 2712 participants, the median age was 68 years, and 50.4% were women. Participants in the group with higher TAC levels had relatively higher IRT, AFT and DSST scores (P=0.025, P=0.008, P<0.001, respectively). In adjusted weighted linear regression, log-transformed TAC was positively associated with AFT (β=1.10, 95%CI: 0.51, 1.70) and DSST (β=2.81, 95%CI: 1.16, 4.45). Compared with the first quartile, the participants in the second (Q2 vs. Q1, OR=0.66, 95%CI: 0.43,1.02) and fourth quartile (Q4 vs. Q1, OR=0.47, 95%CI:0.28, 0.78) of log-transformed TAC showed a decreased risk of impaired cognitive function (ICF) after adjusting for confounders. The dose-response analysis indicated a gradual descent in the risk of ICF as TAC increases. Diabetes mellitus (DM) mediated part of the effect of TAC on ICF. The relationship between TAC and ICF was more pronounced in subjects with DM (Q4 vs Q1, OR=0.36, 95%CI:0.17, 0.74). Conclusion: Our findings support that higher dietary antioxidant potential was related to a decreased risk of cognitive dysfunction, particularly in the subjects with DM who may have oxidative injury. DM was one of the factors mediating the effect of TAC on ICF. [ABSTRACT FROM AUTHOR]

This document is a retraction note from the journal Scientific Reports regarding an article titled "The role of ascorbic acid combined exposure on Imidacloprid-induced oxidative stress and genotoxicity in Nile tilapia." The editors have retracted the article due to concerns raised about the data presented in Figures 4 and 6. The panels in these figures appear to have duplicated features, and the authors' provided raw data was insufficient to address these concerns. Some of the authors do not agree with the retraction, while others did not respond to correspondence from the editor. [Extracted from the article]

Oxidative stress is a well-accepted etiological mechanism that contributes to neuronal dysfunction. Role of oxidative stress as a mechanism of retinopathy in controlled type 2 diabetic patients was evaluated. Participants were divided into three groups: Group 1 as 30 normal eyes of 15 subjects, Group 2 comprised 24 eyes of 12 diabetic patients without retinopathy and Group 3 comprised 23 eyes of 12 diabetic patients with different grades of retinopathy (8 eyes with maculopathy). A complete ophthalmological examination was performed. Oxidative stress markers were measured in blood. Macular thickness was different in all quadrants among all groups and showed a tendency to increase in Group 3 due to diabetic retinopathy with insignificant changes in parapapillary retinal nerve fiber layer thickness although thinning was noted also with retinopathy. Non-significant differences in GST and lipid peroxide levels were observed between the three studied groups, whereas vitamin C and GSH levels were higher in diabetic patients when compared to those in controls. As oxidative stress, hyperglycemia and local inflammation are involved in the pathogenesis of DR, the present study proved that the progressive damage can be retarded in controlled type 2 diabetic patients using different treatment modalities that abated oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Hypovitaminosis C and vitamin C deficiency are common in critically ill patients and associated with organ dysfunction. Low vitamin C status often goes unnoticed because determination is challenging. The static oxidation reduction potential (sORP) reflects the amount of oxidative stress in the blood and is a potential suitable surrogate marker for vitamin C. sORP can be measured rapidly using the RedoxSYS system, a point-of-care device. This study aims to validate a model that estimates plasma vitamin C concentration and to determine the diagnostic accuracy of sORP to discriminate between decreased and higher plasma vitamin C concentrations. Methods: Plasma vitamin C concentrations and sORP were measured in a mixed intensive care (IC) population. Our model estimating vitamin C from sORP was validated by assessing its accuracy in two datasets. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were constructed to show the diagnostic accuracy of sORP to identify and rule out hypovitaminosis C and vitamin C deficiency. Different cut-off values are provided. Results: Plasma vitamin C concentration and sORP were measured in 117 samples in dataset 1 and 43 samples in dataset 2. Bias and precision (SD) were 1.3 ± 10.0 µmol/L and 3.9 ± 10.1 µmol/L in dataset 1 and 2, respectively. In patients with low plasma vitamin C concentrations, bias and precision were − 2.6 ± 5.1 µmol/L and − 1.1 ± 5.4 µmol in dataset 1 (n = 40) and 2 (n = 20), respectively. Optimal sORP cut-off values to differentiate hypovitaminosis C and vitamin C deficiency from higher plasma concentrations were found at 114.6 mV (AUC 0.91) and 124.7 mV (AUC 0.93), respectively. Conclusion: sORP accurately estimates low plasma vitamin C concentrations and can be used to screen for hypovitaminosis C and vitamin C deficiency in critically ill patients. A validated model and multiple sORP cut-off values are presented for subgroup analysis in clinical trials or usage in clinical practice. [ABSTRACT FROM AUTHOR]

Imidacloprid (Imid), a systemic neonicotinoid insecticide, is broadly used worldwide. It is reported to contaminate aquatic systems. This study was proposed to evaluate oxidative stress and genotoxicity of Imid on Nile tilapia (Oreochromis niloticus) and the protective effect of ascorbic acid (Asc). O. niloticus juveniles (30.4 ± 9.3 g, 11.9 ± 1.3 cm) were divided into six groups (n = 10/replicate). For 21 days, two groups were exposed to sub-lethal concentrations of Imid (8.75 ppm, 1/20 of 72 h-LC50 and 17.5 ppm, 1/10 of 72 h-LC50); other two groups were exposed to Asc (50 ppm) in combination with Imid (8.75 and 17.5 ppm); one group was exposed to Asc (50 ppm) in addition to a group of unexposed fish which served as controls. Oxidative stress was assessed in the liver where the level of enzymatic activities including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in addition to mRNA transcripts and, Lipid peroxidation (LPO) were evaluated. Moreover, mitotic index (MI) and comet assay were performed, in addition, the erythrocytic micronucleus (MN), and nuclear abnormalities (NA) were observed to assess genotoxicity in fish. Imid exposure induced significant (p ˂ 0.05) changes in the antioxidant profile of the juveniles' liver by increasing the activities and gene expression of SOD, CAT and GPX as well as elevating the levels of LPO. DNA strand breaks in gill cells, erythrocytes and hepatocytes along with erythrocytic MN and NA were also significantly elevated in Imid-exposed groups. MI showed a significant (p ˂ 0.05) decrease associated with Imid exposure. Asc administration induced a significant amelioration towards the Imid toxicity (8.75 and 17.5 ppm). A significant protective potency against the genotoxic effects of Imid was evidenced in Asc co-treated groups. Collectively, results highlight the importance of Asc as a protective agent against Imid-induced oxidative stress and genotoxicity in O. niloticus juveniles. [ABSTRACT FROM AUTHOR]

Objectives: To study vitamin C levels in children with transfusion-dependent β-thalassemia and correlate with age, transfusions received and iron overload; and to study the effect of administering vitamin C on its levels and Malondialdehyde (MDA) in deficient patients. Methods: This case-control study enrolled 100 children with transfusion-dependent β-thalassemia and 30 healthy controls. MDA levels before and after administration of vitamin C were performed randomly in 36 children with low vitamin C levels. Results: 81/95 (85.3%) study subjects vs none in control group, had low plasma vitamin C levels (P<0.001). Vitamin C levels were low in 64 of 71 (74.7%) subjects with dietary deficiency, while none of the 19 (63.3%) controls with dietary deficiency had low levels (P=0.04). Increasing serum ferritin values correlated with vitamin C deficiency (P=0.02). The mean level of MDA reduced (P<0.001) with vitamin C supplementation. Conclusions: Low levels of vitamin C are common in children with thalassemia. Dietary counseling along with supplementation with vitamin C, in those with low levels may prevent oxidative stress. [ABSTRACT FROM AUTHOR]

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Background and objective: The wheatgrass juice (WGJ) contains a high concentration of vitamin C. WGJ contains a lot of highly functional nutritive ingredients potent to unify the liver with the kidneys for detoxification of the organs and filtration of the blood to build a strong immune system. Also, it boosts fertility and increases sexual desire because of the high magnesium content in phytochemical pigment (chlorophyll) which boosts the production of the enzymes that restores sex steroids. Materials and methods: The experimental animals were divided into 3 groups of 8 rats. The first group (G1) was fed on the standard normal diet. The same feeding was used also in the second group (G2) and third group (G3). But in the G2, a pharmaceutical formula (contain zinc and vitamin A) was used as a food supplement to increase fertility, and in the G3, wheatgrass juice of 11 mg/day was applied. Hunter L, a, and b values; glucose, fructose, and sucrose contents; pH; total soluble solids (TSS); acidity; concentration of vitamin C and vitamin B complex contents; and phenolic compounds of wheatgrass quality juice were measured. Results: The juice samples showed L* value of 21.78 (as a lightness index), a* value of − 7.11 (as a redness index), b* values of 17.35 (as a yellowness index), pH (6.7), TSS (5°Bx), and acidity (0.00992%). In the same time, wheatgrass chlorophyll represents 70% of its total chemical constituents that is an antioxidant and rebuilds the bloodstream. In addition, it gives the juice its distinctive green color which is the major quality factor in juice products. The results amounted to normal values of vital organs such as the liver and kidney functions in all groups. The values of aspartate aminotransferase (AST) were 27.88 ± 2.10, 22.50 ± 4.93, and 23.25 ± 4.71 μ/ml in G1, G2, and G3, respectively. Meanwhile, also the results of sexual hormones indicated an elevation in testosterone hormone in G3 (2.90 ± 0.26 ng/ml) than the normal negative control (2.78 ± 0.23 ng/ml) and pharmaceutical formula positive control (2.04 ± 0.40 ng/ml). However, follicle-stimulating hormone (FSH) decreased to 1.44 ± 0.28 IU/L and 1.45 ± 0.24 for G3 and G2, respectively, compared to 1.65 ± 0.23 IU/L in G1. Conclusion: The findings proved that WGJ increased fertility and promoted youthfulness, and the wheatgrass (WG) has the potential to be used as a "functional herb" containing natural bioactive compounds. [ABSTRACT FROM AUTHOR]

Non-covalent functionalized reduced graphene oxide (rGO) with l-tryptophan was rapidly fabricated by reducing graphene oxide (GO), using l-ascorbic acid as reducer under microwave heating. Atomic force microscope, scanning electron microscope, ultraviolet-visible spectroscopy, X-ray diffraction, Raman spectroscopy and Fourier transform infrared spectroscopy were employed to investigate the morphologies and structures of the samples. The average particle sizes and zeta potentials of rGO were measured by means of dynamic light scattering spectroscopy. Furthermore, the maximum dispersibility of rGO dispersion was calculated from Lambert-Beer law. It was shown that oxidative debris of GO were cleaned after ammonia wash process, and ultimately improving the water dispersibility through enhancing the π-π interaction between l-tryptophan molecules and rGO sheets. The maximum dispersibility of the functionalized rGO dispersion with cleaning oxidative debris was increased by 95 % (from 0.44 to 0.86 mg mL) compared to that without cleaning oxidative debris. This investigation proposed an effective method to fabricate the non-covalent functionalized rGO, as well as the method to improve its water dispersibility. [ABSTRACT FROM AUTHOR]

In this work, we present a novel ascorbic acid (AA) sensor applied to the detection of AA in human sera and pharmaceuticals. A series of Au nanoparticles (NPs) and graphene oxide sheets (Au NP/GO) composites were successfully synthesized by reduction of gold (III) using sodium citrate. Then the Au NP/GO composites were used to construct nonenzymatic electrodes in practical AA measurement. The electrode that has the best performance presents attractive analytical features, such as a low working potential of +0.15 V, a high sensitivity of 101.86 μA mM-1 cm-2 to AA, a low detection limit of 100 nM, good reproducibility and excellent selectivity. And more,it was also employed to accurately and practically detect AA in human serum and clinical vitamin C tablet with the existence of some food additive. The enhanced AA electrochemical properties of the Au NP/GO modified electrode in our work can be attributed to the improvement of electroactive surface area of Au NPs and the synergistic effect from the combination of Au NPs and GO sheets. This work shows that the Au NP/GO/GCEs hold the prospect for sensitive and selective determination of AA in practical clinical application. [ABSTRACT FROM AUTHOR]

Purpose: Superoxide dismutase (SOD) is an important component of antioxidative defense systems and plays an important role in protecting spermatozoa from oxidative damage. In this study, we assessed seminal SOD activity, its association with semen parameters, and also genetic and non-genetic factors contributing to the determination of SOD activity in infertile men. Methods: Semen samples were obtained from 435 male infertility patients. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay. Four single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 genes were genotyped using OpenArray platform. Results: We found that seminal SOD activity was positively associated with sperm concentration and overall motility, whereas inversely with sperm DNA fragmentation. In addition, infertile men with SOD2 rs4880 CC variants showed a low level of SOD activity when compared with TT carriers (Mean ± SD: 268.3 ± 102.3 and 342.8 ± 98.2, respectively, P = 0.005). Those who consumed vitamin C/E (≥3 times per week) had a significantly higher SOD activity level than those who did not (mean ± SD: 379.8 ± 93.3 and 332.2 ± 94.9, respectively, P = 0.001). Conclusions: Seminal SOD activity and other factors influencing SOD activity play a role in determining sperm fertilization potential and male infertility. [ABSTRACT FROM AUTHOR]

Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype. [ABSTRACT FROM AUTHOR]

Purpose: The present study was designed to test the hypothesis that long-term treatment with hydrogen-rich saline abated testicular oxidative stress induced by nicotine in mice. Methods: The effects of hydrogen-rich saline (6 ml/kg, i.p.), vitamin C (60 mg/kg, i.p.) and vitamin E (100 mg/kg, i.p.) on reproductive system and testicular oxidative levels in nicotine-treated (4.5 mg/kg, s.b.) mice were investigated. Results: It was found that vitamin C and vitamin E attenuated serum oxidative level, but did not lower testicular oxidative levels in mice subjected to chronic nicotine treatment, and did not improve the male reproductive damage and apoptosis induced by nicotine. Different from normal antioxidants, vitamin C and vitamin E, hydrogen-rich saline abated oxidative stress in testis, and protected against nicotine-induced male reproductive damages. Conclusion: Our results first demonstrated that long-term treatment with hydrogen-rich saline attenuated testicular oxidative level and improved male reproductive function in nicotine-treated mice. [ABSTRACT FROM AUTHOR]

Study Design:Experimental, controlled, animal study.Objectives:To assess the effects of vitamins C and E (VCE) treatment on oxidative stress and programmed cell deaths after rat spinal cord injury (SCI), as well as functional recovery.Setting:Taiwan.Methods:Fifty-four Sprague-Dawley rats were used for the experimental procedure. In the sham group, laminectomy at T10 was performed, followed by impactor contusion of the spinal cord. In the control group, only a laminectomy was performed without contusion. Oxidative stress status was assessed by measuring the spinal cord tissue content of superoxide dismutase (SOD) and gluthatione peroxidase (GSH-Px) activities. We also evaluated the effects of combined VCE treatment using western blot to analyze expression of cleaved caspase-3 and microtubule-associated protein light chain 3 (LC3), and the Basso, Beattie and Bresnahan (BBB) scale to evaluate functional outcomes.Results:Combined treatment of VCE significantly counteracted the effects of spinal cord contusion on oxidative stress represented by activities of SOD and GSH-Px (P<0.05). The VCE treatment also significantly enhanced LC3-II expression and decreased cleaved caspase-3 compared with the sham (P<0.05). Furthermore, BBB scores significantly improved in the VCE-treated group compared with the sham group (on day 14 and 28 after SCI; P<0.05).Conclusions:The combined administration of VCE was clearly capable of modulating the antioxidant effects, and of reducing apoptosis and increasing autophagy at the lesion epicenter leading to an improved functional outcome. Use of such clinically ready drugs could help earlier clinical trials in selected cases of human SCIs. [ABSTRACT FROM AUTHOR]

Background and aims: Cadmium (Cd) could activate activity of mitogen-activated protein kinase MPK6 in plants. In this study, we investigated the role of MPK6 in mediating Cd toxicity in plants. Methods: The wild type Arabidopsis plants (WT) and the mpk6- 2 mutants were subjected either 0 (Control) or 10 μM Cd treatment. Kinase activity of MPK6, nitric oxide (NO) level, Cd concentration, and oxidative stress were measured. Results: In WT plants, Cd exposure rapidly stimulated kinase activity of MPK6. However, upon Cd exposure, mpk6- 2 showed better growth than the WT. Although Cd-induced production of NO in roots was greater in WT than in mpk6- 2, there was no difference in Cd concentration between the two plants. Nevertheless, the Cd-induced hydroperoxide burst, lipid peroxidation and loss of membrane integrity, were all more severe in the WT than in mpk6- 2. Foliar applications of antioxidant ascorbic acid, vigorously improved the growth of both the WT and mpk6- 2 under Cd exposure. Thereby the growth difference between these two plants was minimized. Conclusions: Mutation of mpk6 enhances Cd tolerance in plants by alleviating oxidative stress, but did not affect cadmium accumulation in plants. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES:This study examined the effect of weight loss after 3, 6 and 12 months of Roux-en-Y Gastric Bypass (RYGB) on energy intake and on several biomarkers of oxidative stress such as levels of vitamin C, beta-carotene, vitamin E (diet/blood), nitric oxide metabolites (NOx), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and activity of catalase (CAT).SUBJECTS/METHODS:Study with a control group (CG), assessed once, and a bariatric group (BG) assessed at the basal period as well as at 3, 6 and 12 months post-surgery; both groups were composed of 5 men and 31 women (n=36). Age was 38.7±9.4 and 39.6±9.2 years old and body mass index (BMI) was 22.2±2.1 and 47.6±9.1 kg/m2, respectively. The variance measure quoted was SEM.RESULTS:The body weight at 12 months was 35.8±1.0% (P<0.001) lower than that of the basal period. At the basal period BG showed higher levels of NOx (P=0.007) and TBARS (P<0.001) and lower levels of vitamins C and E (P<0.001) compared with CG. After 3 months the activity of MPO was decreased (P<0.001). Six months after surgery GSH levels were decreased (P=0.037), whereas CAT activity was increased (P=0.029). After 12 months levels of NOx (P=0.004), TBARS (P<0.001), beta-carotene (P<0.001) and vitamin E (P<0.001) were decreased, whereas those of vitamin C (P<0.001) were increased compared with controls.CONCLUSION:RYGB followed by a daily vitamin supplement apparently attenuated pro-inflammatory and oxidative stress markers 1 year after surgery, but additional antioxidant supplementation appears necessary. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of aerobic training in the context of antioxidant supplementation on systemic oxidative stress and leukocytes heat shock protein (Hsp)72 expression in the elderly. Design: Sixteen septuagenarians (8 males and 8 females, mean age 74.6) were supplemented with Vitamin C and E (respectively 500 and 100mg per day) and randomly assigned either to sedentary (AS) or individualized aerobically trained (AT) group for 8 weeks. Methods: Plasma Vitamin C and E concentrations and aerobic fitness, as well as resting and post graded exercise (GXT) Hsp72 expression in leukocytes, plasma levels of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) were measured pre and post training / supplementation. Results: At the end of the intervention, the two groups showed a significant increase in resting plasma vitamin C and E (approximately 50 and 20% increase respectively) and a significant decrease in both resting and post GXT plasma TBARS and AOPP (approximately 25 and 20% decrease respectively). These changes were of similar magnitude in the two groups. The reduced oxidative stress was concomitant with a 15% decreased expression of Hsp72 in monocytes and granulocytes in both groups. Conclusion: This study provides evidence that in elderly, increased concentration of antioxidant vitamins C and E is associated with a reduction in oxidative stress and leukocytes Hsp72. In this context, 8 weeks of aerobic training has no impact on oxidative stress or leukocytes Hsp72 expression in elderly people. [ABSTRACT FROM AUTHOR]

Abstract: Free radicals interact with other molecules within cells. This can cause oxidative damage to proteins, membranes and genes. Oxidative damage has been implicated in the cause of many diseases such as cancer and Alzheimer’s and has an impact on the body’s aging process. External factors such as pollution, sunlight and smoking also trigger the production of free radicals and the process of programmed cell death (PCD) that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. The study was conducted to 42 male Orycytolagus Cuniculus rabbits. These animals were subdivided into seven groups approaching the comparison between treatment with vitamin C and Di-Mercapto Succinic Acid (DMSA) including positive and negative control groups. Lead ions concentration in blood, liver, kidney and brain were measured before and after treatments application. Apoptotic related proteins P53 and Bcl2 were estimated beside histological studies of tissues. Results revealed that it is more saving to use vitamin C as a lead chelator than DMSA. It is also can be stated that severe lead toxicity can be carcinogenic by increasing the oxidative stress in the biological systems as well as altering the balanced concentration of the apoptotic proteins. [Copyright &y& Elsevier]

Background/Objectives:Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy is known to increase oxidative stress, which may influence pregnancy outcomes and health of the child.Subjects/Methods:This study investigated whether fruit and vegetable intake modifies the relationship between exposure to PAHs and oxidative stress status during pregnancy. Urinary levels of 2-naphthol and 1-hydroxypyrene (biomarkers of exposure to PAHs), and malondialdehyde (MDA; a biomarker of oxidative stress) were analyzed in 715 pregnant women at 12-28 weeks of gestation. The dietary antioxidant intake during pregnancy was estimated using the 24-h recall method. Urinary 2-naphthol, 1-hydroxypyrene and MDA levels were analyzed by high-performance liquid chromatography-fluorescence detection.Results:The urinary MDA level was positively correlated with the 2-naphthol level (r=0.255, P<0.001) and 1-hydroxypyrene level (r=0.240, P<0.001). Multiple regression analysis after adjustment for covariates revealed that the urinary 1-hydroxypyrene level was positively associated with the MDA level; these positive associations only existed in pregnant women, with either the fruit and vegetable intake or the vitamin C intake in the first tertile (<390.1 g/day) or in the first and second tertiles (<141.5 mg/day), respectively.Conclusions:These results suggest that an adequate maternal intake of fruit, vegetables and vitamin C is beneficial to the defense against the oxidative stress associated with exposure to PAHs in pregnant women. [ABSTRACT FROM AUTHOR]

This study was aimed to examine the effect of vitamin C/E intake alone or combined with resistance training on antioxidant/pro-oxidant status, muscle strength and body composition in an elderly population. Fifty-seven men and women with a mean age of 65.6 ± 3.8 years were recruited and randomized in a double-blind fashion into four groups: control-placebo; resistance training (RT); vitamins C/E supplementation (AS); AS+RT. Oxidative stress status and metabolic and lipid profiles were determined at baseline and after six months. Fat-free mass and fat mass measured by DXA were similar at baseline for all groups. At six month, there was a significant difference among the groups as a function of vitamin E supplementation. Moreover, although there was no effect on pro-oxidative parameters, a significant effect on body composition was noted, but no difference was noted on strength gain. The combination of RT+AS had a positive effect on the plasma antioxidant profile but not on the pro-oxidant status. [ABSTRACT FROM AUTHOR]

Objective: Aging and oxidative stress may lead to enhanced cellular damage and programmed cell death. to study the association of intrinsic apoptosis with age and the effect of antioxidant supplementation on intrinsic and UV-induced apoptosis in children, young and elderly people. Methods: The study was a 2 months, double-blind, randomized trial. Three age groups were studied: children, young adults and elderly people. A total of 274 healthy subjects were allocated to a group supplemented with moderate amounts of retinol, β-carotene, α-tocopherol, ascorbic acid and selenium or placebo. Plasma oxidative stress parameters were detected and apoptosis of lymphocytes was evaluated with TUNEL staining. Results: At baseline, percentages of intrinsic apoptosis were 13.8% and 11.1% in elderly and young people, respectively, both significantly higher than children (6.3%). A decrease of 1.7% and 2.3% in intrinsic apoptosis of lymphocytes was found in the supplemented groups of young and elderly people compared with their control groups (all p values <0.001), but no significant decrease in children. Moreover, percentages UV-induced apoptosis significantly decreased by 1..4%, 1.9% and 3.1% in children, young and elderly people, respectively, compared with control groups after the trial. There were considerable increments in concentrations of plasma β-carotene, retinol, tocopherol, ascorbic acid and selenium in all three treated groups after the supplementation. Conclusions: Young and elderly people have a higher intrinsic apoptosis than children, which was improved by antioxidant supplementation. UV-induced damage was attenuated by the supplementation in all three age groups. [ABSTRACT FROM AUTHOR]

orbic acid (AsA) is the most abundant antioxidant in plants and plays a role in responding to oxidative stress. It has been shown that AsA plays a role in protecting against abiotic stresses. Rice seedlings stressed with 5 μM CdCl showed typical Cd toxicity (chlorosis and increase in malondialdehyde content). Rice seedlings pretreated with heat shock at 45°C (HS) or HO under non-HS conditions resulted in the increase in ascorbic acid (AsA) content and the AsA/dehydroascorbate ratio in rice leaves. Exogenous application of AsA or L-galactonone-1, 4-lactone (GalL), a biosynthetic precursor of AsA, under non-HS conditions, which resulted in an increase in AsA content in leaves, enhanced subsequent Cd tolerance of rice seedlings. Pretreatment with imidazole, an inhibitor of NADPH oxidase, under HS conditions significantly decreased HO and AsA contents in leaves and reduced subsequent Cd tolerance of rice seedlings. We also observed that pretreatment with lycorine, which is known to inhibit the conversion of GalL to AsA, significantly inhibited HS-induced AsA accumulation in leaves and reduced HS-induced protection against subsequent Cd stress of rice stress. It appears that HS- or HO-induced protection against subsequent Cd stress of rice seedlings is mediated through AsA. The time-course analyses of HS in rice seedlings demonstrated that the accumulation of HO preceded the increase in AsA. Based on the data obtained in this study, it could be concluded that the early accumulation of HO during HS signals the increase in AsA content, which in turn protects rice seedlings from oxidative damage caused by Cd. [ABSTRACT FROM AUTHOR]

To determine the effect of ascorbic acid and alpha-tocopherol on oxidative stress and bone mineral density (BMD) in elderly people. A double-blind, controlled clinical assay was carried out in a sample of 90 elderly subjects divided into three age-paired random groups with 30 subjects in each group. Group Tx0 received placebo, group Tx1 received 500 mg of ascorbic acid and 400 IU of alpha-tocopherol, whereas group Tx2 received 1,000 mg of ascorbic acid and 400 IU of alpha-tocopherol, for a 12-month period. We measured thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), superoxide dismutase (SOD), and glutation peroxidase (GPx); BMD was obtained on DXA of hip and spine before and after the 12-month treatment period with supplementation of vitamins C and E. We found a positive correlation between hip-BMD and SOD (r = 0.298, p <0.05) and GPx (r = 0.214, p <0.05). Also, a significantly lower decrease of LPO (p <0.05) was observed as linked with hip bone loss in the Tx2 group than in the Tx0 group. Our findings suggest that that administration of 1,000 mg of ascorbic acid together with 400 IU of alpha-tocopherol could be useful in preventing or aiding in the treatment of age-related osteoporosis. [ABSTRACT FROM AUTHOR]

Background/Objectives:Vitamins can help improve cardiovascular control. In contrast, smoking works in the opposite fashion, reducing the baroreflex control of heart rate (HR) possibly via oxidative stress. High-fat challenges also impair cardiovascular regulation. Whether vitamins have acute beneficial effects on the baroreflex control of HR in smokers is unclear.Subjects/Methods:A randomized, placebo-controlled crossover study in 30 male smokers (34.2±6.9 years). Interventions were: (1) moderate (vitamin C (300 mg) and E (75 IU) and folic acid (1 mg)); (2) high doses of vitamins (vitamin C (2 g) and E (800 IU), and folic acid (5 mg)); or, (3) placebo. Vitamins were ingested with cream (a high-fat challenge) or milk (low-fat control). Four hours later, blood was withdrawn and radial pulse wave forms recorded via tonometry. Spontaneous beat-to-beat variations in HR and systolic blood pressure (SBP) were analysed by spectral analysis techniques and sympathovagal control of HR and baroreflex sensitivity (BRS) were assessed.Results:High doses of vitamins increased plasma vitamin C, E and folic acid levels (P<0.05) with no change in SBP, HR or BRS (P>0.05, analysis of variance). Plasma vitamin levels did not correlate with any cardiovascular parameters. Moderate vitamins increased the vagal control of HR (+23%; P<0.05) and cream led to small increases (P<0.05) in SBP (+2 mm Hg) and HR (+2 beats min−1) with no change in BRS.Conclusions:In male smokers, circulating antioxidants had no effect on BRS and minor effects on the cardiovascular system were seen following acute fat and vitamin ingestion.European Journal of Clinical Nutrition (2009) 63, 246–252; doi:10.1038/sj.ejcn.1602912; published online 26 September 2007 [ABSTRACT FROM AUTHOR]

Ascorbate (AsA) is a major antioxidant and free-radical scavenger in plants. Monodehydroascorbate reductase (MDAR; EC 1.6.5.4) is crucial for AsA regeneration and essential for maintaining a reduced pool of AsA. To examine whether an overexpressed level of MDAR could minimize the deleterious effects of environmental stresses, we developed transgenic tobacco plants overexpressing Arabidopsis thaliana MDAR gene ( AtMDAR1) in the cytosol. Incorporation of the transgene in the genome of tobacco plants was confirmed by PCR and Southern-blot analysis and its expression was confirmed by Northern- and Western-blot analyses. These transgenic plants exhibited up to 2.1-fold higher MDAR activity and 2.2-fold higher level of reduced AsA compared to non-transformed control plants. The transgenic plants showed enhanced stress tolerance in term of significantly higher net photosynthesis rates under ozone, salt and polyethylene glycol (PEG) stresses and greater PSII effective quantum yield under ozone and salt stresses. Furthermore, these transgenic plants exhibited significantly lower hydrogen peroxide level when tested under salt stress. These results demonstrate that an overexpressed level of MDAR properly confers enhanced tolerance against ozone, salt and PEG stress. [ABSTRACT FROM AUTHOR]

Ultraviolet-B (UV-B) radiation has a negative impact on plant cells, and leads to the generation of reactive oxygen species (ROS). Heme oxygenase (HO, EC 1.14.99.3) plays a protective role against oxidative stress in mammals, but little is known about this issue in plants. Here, we report for the first time the response of HO in leaves of soybean ( Glycine max L.) plants subjected to UV-B radiation. Under 7.5 and 15 kJ m−2 UV-B doses, HO, catalase (CAT, EC 1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11) activities were increased and the production of thiobarbituric acid reactive substances (TBARS) regain control values after 4 h of plant recuperation. Treatment with 30 kJ m−2 UV-B provoked a decrease in these antioxidant enzyme activities. Immunoblot analysis showed a 4.3 and 3.7-fold increase in HO-1 protein expression after irradiation with 7.5 and 15 kJ m−2, respectively. HO-1 transcript levels were enhanced (up to 77%) at these doses, as assessed by semi-quantitative RT-PCR. These data demonstrated that increased HO activity was associated with augmented protein expression and transcript levels. Plants pre-treated with the antioxidant ascorbic acid did not show the UV-B-induced up-regulation of HO-1 mRNA, but hydrogen peroxide treatment could mimic this reaction. Our results indicate that HO is up-regulated in a dose-depending manner as a mechanism of cell protection against oxidative damage and that such response occurred as a consequence of HO-1 mRNA enhancement involving ROS. [ABSTRACT FROM AUTHOR]

Objective:We have investigated the influence of vitamin C diet supplementation on the antioxidant response and nitrite levels in lymphocytes and erythrocytes during diving apnea.Subjects:Seven male professional apnea divers participated in a double blind crossover study. Divers were randomly assigned to either vitamin C supplemented or placebo groups. The subjects did not take any other supplements than the ones provided for this study.Intervention:One group was supplemented with vitamin C capsules (1 g per day) for 7 days while the other group took a placebo composed of lactose. The usual dietary habits of participants were assessed using a self-reported 7-days 24-h recall before the day of the study. Blood samples were taken under basal conditions, immediately after diving apnea for 4 h and after 1 h of recovery.Results:Catalase activity increased in erythrocytes (23%) and superoxide dismutase increased in lymphocytes (35%) during the recovery only in the placebo group. Lymphocyte ascorbate levels increased in the supplemented group after diving (85%) and maintained high at recovery. Plasma nitrite levels increased about twofold in both groups during the recovery. Erythrocyte nitrite levels increased after diving (50%) and about twofold during the recovery in the supplemented group. Nitrite levels and iNOS levels in lymphocytes were higher in the placebo group than in the supplemented during the recovery. Erythrocyte carbonyl derivates were unchanged in all situations.Conclusions:Vitamin C supplementation influenced the antioxidant response and NO handling in erythrocytes and lymphocytes to the oxidative stress induced by hypoxia–reoxygenation.European Journal of Clinical Nutrition (2006) 60, 838–846. doi:10.1038/sj.ejcn.1602388; published online 15 February 2006 [ABSTRACT FROM AUTHOR]

l-Galactono-1,4-lactone dehydrogenase (GalLDH; EC 1.3.2.3) is the last enzyme in the putativel-ascorbic acid (AsA) biosynthetic pathway of plants. Here, we show for the first time that the overexpression of GalLDH can increase AsA content in tobacco (Nicotiana tabacumL.) BY-2 cells. To see the effect, we analyzed the properties of these AsA-overproducing transgenic cell lines, especially in relation to AsA content of cells, cell division, senescence and resistance to oxidative stress. The mitotic index in AsA-overproducing cells was higher than in wild-type cells. Moreover, the browning of these cells was markedly restrained, and the proportion of dead cells was reduced, especially in the later period of culture. These AsA-overproducing cells also acquired resistance to paraquat (methyl viologen), which produces active oxygen species. These results contribute to the previous insights about AsA and raise the possibility of the generation of plants that have resistance to environmental stresses by increasing their AsA content. [ABSTRACT FROM AUTHOR]

The aim of the study is to determine and to compare the oxidative and antioxidative status of penile corpus cavernosum and peripheral venous blood. A total of 28 adult healthy males were included in the study. Whole blood was simultaneously withdrawn from penile corpus cavernosum and the cubital vein and their plasma separated. Total antioxidant capacity (TAC), vitamin C, total protein, albumin, uric acid, bilirubin and total peroxide (TP) levels of both plasma samples were measured and compared. While TAC, total protein, albumin, bilirubin and uric acid levels were higher, vitamin C levels were lower in cavernosal blood than that of peripheral blood. On the other hand, TP level was found to be higher in penile blood samples than that of peripheral blood. We thought that the normal erectile process of the penile cavernosal body leads to increased production of oxidants as in the mechanism of ischaemia-reperfusion; however, the increase of TAC can prevent development of oxidative injury.International Journal of Impotence Research (2005) 17, 19-22. doi:10.1038/sj.ijir.3901262 Published online 14 October 2004 [ABSTRACT FROM AUTHOR]

Objective: It has been known that maternal oxidative stress during pregnancy plays an important role in fetal growth. However, the association between antioxidant vitamin levels and birth outcomes is not conclusive. We investigated the relationship between maternal serum levels of vitamins C and E during the second trimester and birth weight and length. Design: Prospective cohort study. Setting: Outpatient-clinic of obstetrics, Ewha Womans University Hospital, South Korea. Subjects and methods: The study subjects were 239 healthy, pregnant women who visited an obstetric clinic for antenatal care, and their singleton live births, in Seoul, Korea, between August 2001 and March 2003. We measured the levels of vitamins C and E in maternal serum during the period 24–28 gestational weeks. Each woman was interviewed for dietary intake by trained interviewers during the second trimester. Results: The serum concentration of maternal vitamin C during the second trimester was significantly associated with birth weight and length in the group of full-term deliveries. An increase of 1 μg/ml in the serum vitamin C level increased the birth weight by 27.2 g and the birth length by 0.17 cm. When we considered the levels of vitamins C and E together in the relationship with birth weight and length, we found that the heaviest birth weight and the longest birth length belonged to the group of upper vitamin C/upper vitamin E. However, dietary intake estimated by 24-h recall method was not a predictor of the levels of serumvitamins C and E. Conclusion: We found that maternal serum vitamin C levels during the second trimester were positively correlated with birth weight and length in full-term babies. We also found that birth weight and length were highest when the levels of both vitamins C and E were high. Our results indicate the importance of antioxidant nutrient balance for pregnant women who are exposed to various oxidants through food, drinking water, or inhaled air. [ABSTRACT FROM AUTHOR]

Cadmium is au environmental and industrial pollutant that affects the male reproductive system of humans and animals. However, the mechanism of its adverse effect on Leydig cell steroidogenesis remains unknown. The present study points to the possible involvement of oxidative stress in the suppression of steroidogenesis. Cadmium administration caused an increase in reactive oxygen species (ROS) by elevating testicular malondialdehyde (MDA) and decreasing the activities of testicular antioxidant enzymes such as glutathione peroxidase and superoxide dismutase. The mRNA of Steroid Acute Regulatory (StAR) protein was substantially reduced. The activities of testicular Δ5-3β and 17-β-hydroxysteroid dehydrogenases (HSD) as well as serum testosterone level were also lowered, suggesting that cadmium-induced ROS inhibit testicular steroidogenesis. Supplementation with vitamin C (VC) and or vitamin E (VE) reduced testicular ROS and restored normal testicular function in Cd-exposed rats. We conclude that VC and VE prevent oxidative stress and play vital roles in co-regulating StAR gene expression and steroid production in cadmium-exposed rats. [ABSTRACT FROM AUTHOR]

Ascorbic acid (20.4 g l-1 in 50 h) was synthesized directly from glucose by Xanthomonas campestris as an adaptive response to induced free-radicals through HOCl treatment. Identity of ascorbic acid was confirmed through IR and NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Increased generation of reactive oxygen species, coupled with impaired endogenous scavenging mechanisms, plays a prominent role in the aetiology of neurovascular abnormalities in experimental diabetes mellitus. We examined the efficacy of the natural anti-oxidants vitamins C, E and Β-carotene in preventing nerve conduction and nutritive blood flow deficits in streptozotocin-diabetic rats. One month of diabetes caused a 19.1% reduction in sciatic motor conduction velocity ( p<0.001). This was approximately prevented 80-90% by high-dose (1000 mg · kg · day) vitamin E and Β-carotene treatments ( p<0.001). Vitamin C had lesser effects; the maximum protection found for motor conduction velocity was 36% using a dose of 150 mg · kg · day ( p<0.001). High dose (500 mg · kg · day) vitamin C had a lesser effect on conduction than intermediate doses. Joint vitamin C and lower dose (500 mg · kg · day) vitamin E treatment had a predominantly additive preventive effect against nerve dysfunction. Resistance to hypoxic conduction failure for sciatic nerve in vitro was markedly increased by diabetes and this remained relatively unaffected by treatment. Sciatic nutritive endoneurial blood flow, measured using microelectrode polarography and hydrogen clearance, was reduced 46.1% by 1 month of diabetes ( p<0.001). This was prevented to the extent of 87%, 36% and 98% by vitamins E, C and Β-carotene, respectively ( p<0.01). These data emphasize the role of oxidative stress in the development of early neurovascular changes in experimental diabetes and show that naturally available scavengers have a neuroprotective action. [ABSTRACT FROM AUTHOR]

Background: Mercury has been documented as an industrial risk that posed a serious danger to human health. Mercury exposure results in oxidative stress that may lead to the pathogenesis of male reproductive dysfunction. The present study investigated the ameliorating potential of Chenopodium album L. and vitamin C against mercuric chloride-induced oxidative deterioration of reproductive functions in adult male rats. Methods: Group 1 (control) received saline. Group 2 received Mercury (0.15 mg/kg b.w, i.p) dissolved in distilled water. Groups 3 and 4 were given oral gavage of vitamin C (200 mg/kg b.w) and the ethanolic extract of C. album (200 mg/kg b.w) respectively, along with Mercury (0.15 mg/kg b.w, i.p). Group 5 was treated only with C. album (200 mg/kg b.w). After 30 days of the treatment, the rats were dissected and their testicular tissue and the cauda epididymis were used for biochemical analysis while blood plasma was used for protein determination. Results: The applied dose-treatment of Mercury-induced oxidative stress in the testis and cauda epididymis tissues of the rats was apparent by a noteworthy decrease in total protein, CAT, SOD, POD, and GST values while there was increase in ROS and TBARS levels. Furthermore, Mercury decreases daily sperm production and enhanced sperm DNA damage as noticeable by an increase in the head and tail length of comets and decrease in intact DNA. There was no significant effect on the body weight and the weight of the reproductive tissues. Treatment with C. album significantly ameliorated the total protein, ROS, and TBARS content. Similarly, the level of CAT, SOD, POD, and GST was significantly improved and the daily sperm production was significantly increased. Furthermore, C. album administration significantly protected Mercury-induced sperm DNA damage. The results of the extract treatment group were compared with those of vitamin C in detoxifying the oxidative stress and restoring the sperm parameters. Conclusion: C. album showed protection against Mercury-induced oxidative stress by ameliorating antioxidant enzyme activity, daily sperm production, and DNA damage in rat testes. This suggests that C. album could be beneficial against toxicity induced by an environmental toxicant. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells (hMSCs) contribute to ischemic tissue repair, regeneration, and possess ability to self-renew. However, poor viability of transplanted hMSCs within ischemic tissues has limited its therapeutic efficiency. Therefore, it is urgent to explore new method to improve the viability of the grafted cells. By using a systematic analysis, we reveal the mechanism of synergistic protection of N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) on hMSCs that were under H2O2-induced oxidative stress. The combined treatment of NAC and AAP (NAC/AAP) reduces reactive oxygen species (ROS) generation, stabilizes mitochondrial membrane potential and decreases mitochondrial fission/fragmentation due to oxidative stress. Mitochondrial fission/fragmentation is a major prologue of mitoptosis. NAC/AAP prevents apoptotic cell death via decreasing the activation of BAX, increasing the expression of BCL2, and reducing cytochrome c release from mitochondria that might lead to the activation of caspase cascade. Stabilization of mitochondria also prevents the release of AIF, and its nuclear translocation which may activate necroptosis via H2AX pathway. The decreasing of mitoptosis is further studied by MicroP image analysis, and is associated with decreased activation of Drp1. In conclusion, NAC/AAP protects mitochondria from H2O2-induced oxidative stress and rescues hMSCs from mitoptosis, necroptosis and apoptosis. [ABSTRACT FROM AUTHOR]