Erythrocyte Glutathione Levels Research Articles

Effect of vitamin C upon Selective Serotonin Reuptake Inhibitors (SSRIs) treated Obsessive Compulsive Disorder Patients: A randomized controlled clinical trial in Bangladesh

Objective: To assess the efficacy of vitamin C as an adjunct to Selective Serotonin Reuptake Inhibitors (SSRIs) intreating OCD patients. Design: Single-blind randomized controlled trial. Study eligibility: Randomly selected 96 OCD patients diagnosed by the psychiatric consultants following the DSM-5criteria of both sexes aged 18 years and above were initially enrolled; finally, 83completed the study. The study wasconducted at Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka, Bangladesh, from March 2018 toFebruary 2019. Interventions: After obtaining written informed consent, participants were randomly divided into group A (controlgroup) and group B (intervention group). A baseline recording of the body's endogenous antioxidant markers (plasmavitamin C and erythrocyte glutathione levels), oxidative stress marker (plasma malondialdehyde), and Yale-Brownscore of OCD by Yale-Brown Obsessive-Compulsive Scale(Y-BOCS) were measured in both groups. The control group(n=40) received oral SSRIs daily for eight weeks, while the intervention group (n=56) received the SSRIs plus oralvitamin C (500 mg twelve hourly) daily for the same duration. The biochemical parameters and the Y-BOCS score ofOCD of both groups were obtained after eight weeks, and the result was analyzed and compared.Main outcome measures: The outcomes were levels of plasma vitamin C, erythrocyte (RBC) glutathione and plasmamalondialdehyde, and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Result: Baseline recordings suggest significantly (p<0.05) lower levels of plasma vitamin C and RBC glutathioneconcentrations and non-significant (p>0.05) higher levels of plasma MDA concentrations in both groups. After eightweeks of intervention with vitamin C plus SSRIs, plasma vitamin C and RBC glutathione levels were significantly(p<0.001) increased more in the intervention group compared to the control group (97.26% vs 44.44% and 57% vs44.16%, respectively). On the other hand, plasma MDA concentrations and the mean Y-BOCS score were reduced morein the intervention group compared to their counterpart (48.15% vs 37.74% and 29.69% vs 21.74%; p<0.001). Conclusion: The result showed that vitamin C adjunct to SSRIs in OCD patients had significantly improved vitamin Cand RBC glutathione concentrations, while the plasma MDA level and the Y-BOCS score were decreased in theintervention group. Treatment with vitamin C leads to a more significant improvement in OCD symptoms.Trial registration: Registered with Clinical Trials. Gov (NCT03754647). Bangladesh Crit Care J March 2023; 11 (1): 24-30

Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?

Telomeres are repetitive DNA sequences at the end of chromosomes that protect them from degradation. They have been the focus of intense research because short telomeres would predict accelerated ageing and reduced longevity in vertebrates. Oxidative stress is considered a physiological driver of the telomere shortening and, consequently, short lifespan. Among molecules fighting against oxidative stress, glutathione is involved in many antioxidant pathways. Literature supports that oxidative stress may trigger a compensatory "hormetic" response increasing glutathione levels and telomere length. Here, we tested the link between total glutathione concentration and telomere length in captive birds (zebra finches; Taeniopygia guttata). Total glutathione levels were experimentally decreased during birds' growth using a specific inhibitor of glutathione synthesis (buthionine sulfoximine; BSO). We monitored the birds' reproductive performance in an outdoor aviary during the first month of life, and their longevity for almost 9 years. Among control individuals, erythrocyte glutathione levels during development positively predicted erythrocyte telomere length in adulthood. However, BSO-treated females, but not males, showed longer telomeres than control females in adulthood. This counterintuitive finding suggests that females mounted a compensatory response. Such compensation agrees with precedent findings in the same population where the BSO treatment increased growth and adult body mass in females but not males. BSO did not influence longevity or reproductive output in any sex. However, early glutathione levels and adult telomere length interactively predicted longevity only among control females. Those females with "naturally" low (non-manipulated) glutathione levels at the nestling age but capable of producing longer telomeres in adulthood seem to live longer. The results suggest that the capability to mount a hormetic response triggered by low early glutathione levels can improve fitness via telomere length. Overall, the results may indicate a sex-specific link between glutathione and telomere values. Telomerase activity and sexual steroids (estrogens) are good candidates to explain the sex-biased mechanism underlying the early-life impact of oxidative stress on adult telomere length.

Effect of supplemental methyl sulfonyl methane on performance, carcass and meat quality and oxidative status in chronic cyclic heat-stressed finishing broilers

Methyl sulfonyl methane (MSM) is available as a dietary supplement for human and has been associated with multiple health benefits such as reduction of oxidative stress. Heat stress (HS) is an environmental stressor challenging poultry production and known to inflict oxidative stress. We hypothesized that dietary MSM could attenuate HS-induced detrimental effects in broilers mediated by enhancement of antioxidant defenses. Hence, seven hundred ninety-two 1-day-old male Ross 308 broilers were allocated to 3 dietary treatments composed of corn-soybean meal diets with 0 (Ctrl), 1, or 2 g/kg MSM, with 12 replicates (22 birds each) per treatment for 39 d and subjected to a chronic cyclic HS model (temperature of 34°C and 52-58% relative humidity for 6 h daily) from d 24 to 39. MSM at 1 and 2 g/kg linearly increased daily gain and decreased feed-to-gain ratio compared with Ctrl in the grower phase (d 10-21, both P < 0.05). In the finisher phase (d 21-39) none of the performance and carcass indices were affected by treatment (P > 0.05). Nonetheless, data suggest reduced mortality by feeding MSM during HS. Also, during HS the diets with graded levels of MSM resulted in reduced rectal temperatures (P < 0.05) along with linearly decreased panting frequency on d 24 (P < 0.05). MSM supplemented birds showed a trend for linearly decreased thiobarbituric acid reactive substances of breast meat upon simulated retail display (P=0.078). In addition, MSM administration linearly decreased lipid oxidation in plasma (d 25 and 39, P < 0.05) and breast muscle at d 23 (P < 0.05), concomitantly with linearly increased glutathione levels in erythrocytes (d 23 and 39, P < 0.05; d 25, P < 0.1) and breast muscle (d 23, P < 0.05; d 39, P < 0.1). In conclusion, MSM increased growth performance of broilers during grower phase, and exhibited positive effects on heat tolerance mediated by improved antioxidant capacity in broilers resulting in lower mortality in finisher phase.

Increased apoptosis, tumor necrosis factor-α, and DNA damage attenuated by 3',4'-dihydroxyflavonol in rats with brain İschemia-reperfusion.

OBJECTIVES:This research was aimed to find out the effects of 3',4'-dihydroxyflavonol (DiOHF) on apoptosis, DNA damage, and tumor necrosis factor-α (TNF-α) levels in the frontal cortex of rats with induced experimental brain ischemi reperfusion.MATERIALS AND METHODS:A total of 38 Wistar albino male rats were used. Groups were created as 1-Sham; 2-Ischemia-reperfusion (I/R); 3-I/R + DiOHF (10 mg/kg); 4-Ischemia + DiOHF + reperfusion; 5-DiOHF + I/R. I/R was performed by carotid artery ligation for 30 min in anesthesized animals. Following experimental applications, blood samples were taken from anesthetized rats to obtain erythrocyte and plasma. Later, the rats were killed by cervical dislocation, and frontal cortex samples were taken and stored at − 80° C for the analysis.RESULTS:In the ischemic frontal cortex tissue sections degenerate neuron numbers, Terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) positive cell ratio and caspase-3 positive cell ratio increased. Malondialdehyde, TNF-α, and 8-OHdG levels were increased in both plasma and tissue in ischemia group, whereas tissue and erythrocyte glutathione levels were significantly suppressed. However, these values were significantly reversed by DiOHF treatment.CONCLUSION:The results of the study showed that I/R significantly increased apoptosis, TNF-α, and DNA damage in rats with brain I/R. However, 10 mg/kg intraperitoneal DiOHF treatment improved deterioted parameters.

Dietary Cysteine Intake is Associated with Blood Glutathione Levels and Isometric Strength.

Glutathione is the most abundant cellular antioxidant and regulates redox homeostasis. Healthy individuals with certain antioxidant inadequacies/deficiencies exhibit impairments in physiological functions. The aim was to investigate whether low levels of dietary cysteine intake are associated with a) lower erythrocyte glutathione, b) increased plasma F2-isoprostanes, and c) impaired muscle function. Towards this aim, we recorded the dietary intake of the three amino acids that synthesize glutathione (i. e., glutamic acid, cysteine, and glycine) in forty-one healthy individuals, and subsequently measured erythrocyte glutathione levels. Maximal isometric strength and fatigue index were also assessed using an electronic handgrip dynamometer. Our findings indicate that dietary cysteine intake was positively correlated with glutathione levels (r=0.765, p<0.001). In addition, glutathione levels were negatively correlated with F2-isoprostanes (r=- 0.311, p=0.048). An interesting finding was that glutathione levels and cysteine intake were positively correlated with maximal handgrip strength (r=0.416, p=0.007 and r=0.343, p=0.028, respectively). In conclusion, glutathione concentration is associated with cysteine intake, while adequate cysteine levels were important for optimal redox status and muscle function. This highlights the importance of proper nutritional intake and biochemical screening with the goal of personalized nutrition.

Oxidative Stress Experienced during Early Development Influences the Offspring Phenotype.

AbstractOxidative stress (OS) experienced early in life can affect an individual's phenotype. However, its consequences for the next generation remain largely unexplored. We manipulated the OS level endured by zebra finches (Taeniopygia guttata) during their development by transitorily inhibiting the synthesis of the key antioxidant glutathione ("early-high-OS"). The offspring of these birds and control parents were cross fostered at hatching to enlarge or reduce its brood size. Independent of parents' early-life OS levels, the chicks raised in enlarged broods showed lower erythrocyte glutathione levels, revealing glutathione sensitivity to environmental conditions. Control biological mothers produced females, not males, that attained a higher body mass when raised in a benign environment (i.e., the reduced brood). In contrast, biological mothers exposed to early-life OS produced heavier males, not females, when allocated in reduced broods. Early-life OS also affected the parental rearing capacity because 12-day-old nestlings raised by a foster pair with both early-high-OS members grew shorter legs (tarsus) than chicks from other groups. The results indicate that environmental conditions during development can affect early glutathione levels, which may in turn influence the next generation through both pre- and postnatal parental effects. The results also demonstrate that early-life OS can constrain the offspring phenotype.

Antioxidant supplementation, redox deficiencies and exercise performance: A falsification design

The aim of the present study was to validate the idea of personalized redox supplementation by subjecting individuals to targeted and non-targeted antioxidant supplementation schemes. Seventy-three volunteers were screened for plasma vitamin C and erythrocyte glutathione levels. Three groups were formed: i) the “low vitamin C″ group (12 individuals with the lowest vitamin C levels; Low VitC), ii) the “low glutathione” group (12 individuals with the lowest glutathione levels; Low GSH) and iii) a control group (12 individuals with moderate vitamin C and glutathione levels). The three groups received 1 g of vitamin C or 1.2 g of NAC daily for 30 days in a crossover design with a wash-out period of 30 days. Both antioxidant treatments reduced the increased resting systemic oxidative stress levels, assessed via urine F2-isoprostanes, in the Low VitC and Low GSH groups (P < .05). A significant group × time interaction (P < .05) was found for VO2max and isometric peak torque after both treatments, with the Low VitC and Low GSH groups exhibiting improved performance only after the targeted treatment (vitamin C and NAC, respectively). A significant group × time interaction (P < .05) was found for fatigue index after NAC treatment, but not after vitamin C treatment. No interaction was found for the Wingate test after both treatments. Most of the evidence verifies the idea that antioxidant supplementation increases performance when a particular deficiency is reversed. This indicates that the presence of oxidative stress per se does not rationalize the use of antioxidants and emphasizes the need to identify “responsive” phenotypes.

Correlation Between Erythrocyte Glutathione Levels and Severity of Melasma

Background: Melasma is a common acquired disorder of hyperpigmentation, characterized classically by the presence of symmetrical, light-to-dark, muddy-brown macules with borders on the face, especially the forehead, cheeks, upper lip, chin, and nose. Knowledge of an increase in free radicals and decreased antioxidants in patients with melasma led to the belief that oxidative stress is involved in the pathogenesis of melasma. Glutathione (GSH) is an antioxidant that can be used as a parameter to assess the antioxidant-free radical activity in the pathogenesis of melasma. Objectives: The study aimed to determine the correlation between erythrocyte glutathione levels and the severity of melasma. Methods: A case series study was done from May to July 2018 in the Outpatient Clinic of Dermatology and Venereology Department, Dr. Mohammad Hoesin General Hospital Palembang. Thirty female patients met the inclusion criteria. The independent variable was the erythrocyte glutathione level, and the dependent variable was the melasma severity. The diagnosis was established based on clinical examinations, and the severity was determined by the modified Melasma Area Severity Index (mMASI) score. The correlation between variables was analyzed using Spearman Rho’s test (P &lt; 0.05). The data analysis was done with SPSS version 20.0 (SPSS, Inc Chicago, Illinois). Results: Thirty female patients were diagnosed with melasma. The mean mMASI score was 8.72 ± 5.14 (2.0 to 16.9). Most of the participants had mild melasma (46.7%). The mild group had the highest mean erythrocyte glutathione level (4.05 ± 0.63 μmol/g) and the lowest mean erythrocyte glutathione level was in the severe group (1.79 ± 0.16 μmol/g). There was a very strong negative correlation between erythrocyte glutathione levels and melasma severity (r = -0.907; P = 0.000). Conclusions: There was a very strong negative correlation between erythrocyte glutathione levels and melasma severity.

Deneysel Diyabette Döteryum Azlığının Eritrositler Üzerine Etkisi

In the development of diabetic complications, oxidative stress caused by hyperglycemia plays an important role. Deuterium depletion has protective effect against cellular damage and tumor suppressor effect in cancer cell lines. The purpose of this study was to examine and evaluate the effect of deuterium depletion on erythrocyte oxidant and antioxidant system parameters in experimental diabetes induced by streptozotocin (STZ) in rats. On the 30th or 40th day after STZ injection, blood samples were taken and blood glucose levels were measured. Erythrocyte hemolysates were also prepared. Lipid peroxidation and glutathione levels and glutathione-S-transferase, superoxide dismutase and catalase enzyme activities of erythrocytes were determined. At the 30 or 40 day periods, deuterium depleted water (DDW) consumption had differently affected oxidant-antioxidant parameters of erythrocytes. The clear effect of deuterium depletion in drinking water from 150 ppm to 85 ppm was observed in glutathione levels and it increased erythrocyte glutathione levels in both the control and diabetic groups. In conclusion, deuterium depletion may have protective effects on diabetes induced oxidative stress. Further studies are needed to be done to determine the mechanism of action and the useful dosage and the application period of DDW.

Dietary supplementation with annatto food-coloring extracts increases the resistance of human erythrocytes to hemolysis

Erythrocytes exhibit high susceptibility to hemolysis in several pathologies due to the oxidation of cellular components. We hypothesized that annatto carotenoids improve the redox status of erythrocyte plasma membranes and promote a consequent increase in human erythrocyte resistance to hemolysis. The objective of this study was to evaluate whether food-grade annatto carotenoids can increase human erythrocyte resistance to hemolysis in vitro and ex vivo. For the in vitro experiment, erythrocytes from healthy volunteers were isolated and coincubated with bixin (BIX) or norbixin (NBIX) and 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), glucose, or sodium nitrite (NaNO2) as hemolysis inducers. In the ex vivo study, healthy volunteers consumed a capsule containing BIX or NBIX (0.05 mg/kg body weight per day) or placebo for 7 days before blood sample collection. Their erythrocytes were isolated and incubated with AAPH, glucose, or NaNO2. In both the ex vivo and in vitro studies, erythrocytes were subjected to osmotic fragility tests. The activity of antioxidant enzymes, and reduced glutathione and lipid peroxidation levels in erythrocytes were also evaluated ex vivo. In vitro BIX and NBIX not only reduced erythrocyte membrane fragility induced by AAPH, glucose, or NaNO2 but also improved basal osmotic resistance in the micromole-per-liter range (P < .05). BIX and NBIX supplementation increased erythrocyte membrane resistance (P < .05), with BIX being more effective. Also, BIX and NBIX protected erythrocytes from lipid peroxidation and improved the cellular redox environment (P < .05). These results support the hypothesis that annatto carotenoids supplementation exerts antihemolytic properties by preventing the oxidative damage of human erythrocytes.

Identification of Novel Variants Associated with Fetal Hemoglobin Levels in Healthy Donors (the INTERVAL study)

Sickle cell disease (SCD) affects more than five million people worldwide, predominantly in sub-Saharan Africa. Hereditary persistence of fetal hemoglobin (HbF) is an uncommon genetic condition in which production of HbF in early life is not suppressed. SCD symptoms are reduced in patients carrying this condition, suggesting that increased HbF levels may be a promising therapeutic strategy to ameliorate the symptoms of SCD. This is exemplified by the HbF-raising compound hydroxyurea, currently the most commonly used US Food and Drug Administration approved drug treatment for SCD. However, hydroxyurea is only effective in ~70% of patients and carries a black box warning for carcinogenicity, hence there is a need for additional SCD treatments. Previous genome-wide association studies (GWAS) have identified four loci robustly associated with HbF levels, including variants in the BCL11A region. These initial genetic discoveries have led to promising ex vivo gene-editing approaches to silence or reduce levels of BCL11A, which are currently being tested in clinical trials. To identify novel potential therapeutic targets to raise HbF levels, we conducted the largest GWAS of HbF levels in ~11,000 healthy blood donors from the INTERVAL study among whom HbF was measured in whole blood using a mass spectrometry approach. We ran linear mixed models accounting for age, sex, blood group, technical effects and 10 principal components of ancestry for 14,910,742 variants either directly genotyped using the Affymetrix UK Biobank array or imputed from a combined 1000 Genomes/UK10K reference panel. In addition to confirming previously reported signals at the BCL11A, HBS1L-MYB and HBB loci, stepwise conditional analysis identified six novel genomic regions at genome-wide significance (p&lt;5x10-8). At some loci we identified multiple independent association signals, including two at BCL11A, three at HBS1L-MYB, and two at HBB. Genetic fine-mapping resolved some loci to highly likely causal variants (posterior probability&gt;0.5), including a rare (frequency=0.2%) variant near GRIK2. To identify likely causal genes and mechanisms, we integrated our results with relevant transcriptomic and epigenomic datasets. Preliminary results suggest that a common (frequency=26%) 29 base-pair indel upstream of CHAC2 is highly likely (posterior probability=0.77) to be the causal variant at this locus. The variant maps to a site of active chromatin and GATA1 transcription factor binding specifically in erythroblasts, and the insertion allele contains a GATA motif suggesting that this variant regulates HbF levels by the presence or absence of a second GATA1 binding site. Gene expression data across a range of hematopoietic cells revealed a restricted expression pattern of CHAC2 in erythroblasts, but not for other genes in the region, suggesting CHAC2 as the likely causal gene. CHAC2 encodes the glutathione-specific gamma-glutamylcyclotransferase 2, an enzyme that catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide. This finding adds support to the idea that altered erythrocyte glutathione levels play a role in SCD pathogenesis, potentially via HbF modulation. Ongoing work includes characterizing the likely causal mechanisms of the six novel loci, and providing target validation of CHAC2 using genome editing and deep phenotyping of erythroid cells. In summary, our expanded GWAS has identified new loci associated with HbF levels, providing novel potential therapeutic targets for SCD. Disclosures Lessard: Sanofi: Employment. Peters:Sanofi: Employment. Krishnamoorthy:Sanofi: Employment.

A colorimetric method to measure oxidized, reduced and total glutathione levels in erythrocytes

AbstractBackgroundThe most important antioxidant for erythrocytes is glutathione. In this study, a non-enzymatic recycling spectrophotometric method was developed to measure oxidized and reduced glutathione (GSH) levels in erythrocytes. The newly developed method consists of two steps. In the first step, the levels of GSH were determined in the sample. Subsequently, total glutathione levels were measured by reducing the oxidized glutathione (GSSG) with sodium borohydride (NaBH4). Half of the difference between total glutathione and GSH gives the GSSG.ResultsThe new method was linear between 0 and 3000 μmol/L (r2 = 0.999). The percentage recovery measured by the developed method was 100.2 ± 2.4%. The total precision of the total glutathione, GSH and GSSG was 1.26%, 1.02% and 6.65%, respectively. GSH levels were significantly lower in patients with type 2 diabetes mellitus (DM), while GSSG levels were significantly higher (p &lt; 0.05). Hemoglobin A1c(HbA1c) levels were negatively correlated with GSH levels, whereas positively correlated with GSSG (p &lt; 0.05).ConclusionsIn conclusion, this method is easy to apply in routine practice with high accuracy, precision and reproducibility.

The effects of resveratrol administration on lipid oxidation in experimental renal ischemia-reperfusion injury in rats

ABSTRACTWe investigated how resveratrol affects lipid oxidation during experimental renal ischemia-reperfusion injury in rats. We used 48 adult male rats assigned to five groups: group 1, control; group 2, renal ischemia; group 3, renal ischemia + reperfusion; group 4, resveratrol + renal ischemia; group 5, resveratrol + renal ischemia + reperfusion. Plasma and renal tissue malondialdehyde (MDA), and erythrocyte and renal tissue glutathione (GSH) levels were measured and histologic changes in the renal tissue were examined. Ischemia-reperfusion affected the MDA-GSH balance adversely and caused histopathological changes in the renal tissue of the ischemia and ischemia + reperfusion groups. Resveratrol treatment normalized MDA and GSH levels as well as the histopathology that occurred in the renal tissue of the ischemia and ischemia + reperfusion groups.

The Effects of Hyperbaric Oxygen at Different Pressures on Oxidative Stress and Antioxidant Status in Rats.

Background: The optimal use of oxygen at greater than atmospheric pressures in any operational or therapeutic application (hyperbaric oxygen, HBO2) requires awareness of the fact that the beneficial effects of oxygen coexist with toxic effects depending on the pressure and duration of exposure. In this study, we aimed to investigate the effect of HBO2 therapy on oxidative stress and antioxidant status in commonly used protocol for acute HBO2 indications, such as carbon monoxide intoxication, central retinal artery occlusion, crush injury, gas gangrene, and to compare it with normobaric oxygen (NBO2) in healthy rats. Materials and Methods: Fifty-six male, young adult Wistar albino rats were randomly divided into seven groups and named as Group I through Group VII. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), and erythrocyte glutathione (GSH) levels in control group were compared to the levels in other groups. Results: The increases in MDA levels and the decrease in SOD activities were statistically significant in HBO2 groups at the end of the first 24 h when compared to the control group, and the significant decrease in erythrocyte GSH level was only at 2.4 atmospheres absolute. Conclusions: The present study showed that pressure and frequency of exposure are important factors to consider when investigating HBO2-induced oxidative stress and antioxidant response.

Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study.

Older individuals suffer from low NADH levels. We have previously shown that nicotinamide riboside [NR; a NAD(P)(H) precursor] administration impaired exercise performance in young rats. It has been suggested that supplementation of redox agents exerts ergogenic effect only in deficient individuals. We hypothesized that old individuals would more likely benefit from NR supplementation. We investigated the effect of acute NR supplementation on redox homeostasis and physical performance in young and old individuals. Twelve young and twelve old men received NR or placebo in a double-blind cross-over design. Before and 2 h after NR or placebo supplementation, blood and urine samples were collected, while physical performance (VO2max, muscle strength, and fatigue) was assessed after the second blood sample collection. At rest, old individuals exhibited lower erythrocyte NAD(P)H levels, higher urine F2-isoprostanes and lower erythrocyte glutathione levels compared to young (P < 0.05). NR supplementation increased NADH (51% young; 59% old) and NADPH (32% young; 38% old) levels in both groups (P < 0.05), decreased F2-isoprostanes by 18% (P < 0.05), and tended to increase glutathione (P = 0.078) only in the old. NR supplementation did not affect VO2max and concentric peak torque, but improved isometric peak torque by 8% (P = 0.048) and the fatigue index by 15% (P = 0.012) in the old. In contrast, NR supplementation did not exert any redox or physiological effect in the young. NR supplementation increased NAD(P)H levels, decreased oxidative stress, and improved physical performance only in old subjects, substantiating that redox supplementation may be beneficial only in individuals with antioxidant deficiencies.

Mild therapeutic hypothermia decreases oxidative damage and increases glutathione levels in post-cardiac arrest patients

Background The post-cardiac resuscitation syndrome is a pathophysiologic state after the successful cardiopulmonary resuscitation in cardiac arrest patients. Ischemia-reperfusion-induced oxidative stress is one of the main mechanisms of tissue injury after cardiac arrest [1]. A decrease in antioxidant defenses may contribute to ischemia-reperfusion injury [2]. The mild hypothermia treatment may improve the tissue damage in post-cardiac arrest patients [3]. Mild therapeutic hypothermia is known to decrease the levels of oxidative damage biomarkers, as previously shown by our research group [4]. The mechanisms involving cardiac arrest pathophysiology and hypothermia treatment are not well elucidated. Methods Intensive care unit patients admitted in 2011 and 2012, victims of in-hospital or out-of-hospital cardiac arrest were screened for the study. The sample consisted of 31 patients under controlled normothermia (36oC) and 11 patients treated with mild therapeutic hypothermia (33oC). Mild hypothermia was induced 4-5h after successful cardiopulmonary resuscitation for 24 h. Clinical data and venous blood samples were collected 6, 12, 36 and 72 h post-cardiac arrest. We investigated lipid (malondialdehyde levels) and protein (carbonyl levels) damage biomarkers, and also investigated the levels of the antioxidants glutathione, vitamin C and vitamin E, and nitric oxide levels at 6, 12, 36, and 72 h after cardiac arrest. Data were compared by multivariable logistic-regression models with generalized estimating equations and pairwise comparisons of estimated means by the post-hoc Bonferroni method. Results Serum malondialdehyde and plasma carbonyl levels were decreased in hypothermic group at 6, 12, 36, and 72 h after cardiac arrest in hypothermic patients [4]. Also, erythrocyte glutathione levels were elevated by mild therapeutic hypothermia at all time-points, while serum Vitamin C levels decreased significantly at 6 and 12 h after cardiac arrest in hypothermic patients, coinciding with the period of therapeutic hypothermia. Serum vitamin E and erythrocyte nitric oxide levels were not altered by hypothermic treatment. Discussion The present results evidence that hypothermia can reduce oxidative damage in post-cardiac arrest patients. Moreover, our findings reported, for the first time, increased glutathione levels after cardiac arrest in hypothermic patients as compared to all time points in normothermic patients. There is no previous evidence or possible mechanism corroborating a decrease in vitamin C levels as a consequence of hypothermia. Conclusions These findings suggest that mild therapeutic hypothermia may reduce oxidative damage to lipids and proteins, and concomitantly elevate glutathione levels. Therefore, mild therapeutic hypothermia may contribute to the tissues protection from ischemia-reperfusion injury after cardiac arrest by decreasing oxidative stress.

Mild Therapeutic Hypothermia Increases Glutathione Levels in Postcardiac Arrest Patients.

Ischemia-reperfusion (I/R)-induced oxidative stress is one of the main mechanisms of tissue injury after cardiac arrest (CA). A decrease in antioxidant defenses may contribute to I/R injury. The present study aims to investigate the influence of mild therapeutic hypothermia (MTH) on levels of nonenzymatic antioxidants after CA. We investigated antioxidant levels at 6, 12, 36, and 72 hours after CA in central venous blood samples of patients admitted to intensive care. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 hours of MTH (33°C). Erythrocyte glutathione (GSH) levels were elevated by MTH, increasing at 6, 12, 36, and 72 hours after CA in hypothermic patients (mean GSH levels in normothermic patients: 6 hours = 73.89, 12 hours = 56.45, 36 hours = 56.46, 72 hours = 61.80 vs. hypothermic patients: 6 hours = 176.89, 12 hours = 198.78, 36 hours = 186.96, and 72 hours = 173.68 μmol/g of protein). Vitamin C levels decreased significantly at 6 and 12 hours after CA in hypothermic patients (median vitamin C levels in normothermic patients: 6 hours = 7.53, 12 hours = 9.40, 36 hours = 8.56, and 72 hours = 8.51 vs. hypothermic patients: 6 hours = 5.46, 12 hours = 5.44, 36 hours = 6.10, and 72 hours = 5.89 mmol/L), coinciding with the period of therapeutic hypothermia. Vitamin E and nitric oxide levels were not altered by hypothermic treatment. These findings suggest that MTH alters nonenzymatic antioxidants differently, decreasing circulating vitamin C levels during treatment; however, MTH elevates GSH levels, possibly protecting tissues from I/R injury after CA.

Effects of short-term Pilates exercise on selected blood parameters

The aim of our prospective, interventional, pre-post, single arm study was to supplement the lack of knowledge of the effect of short-term Pilates intervention on selected blood parameters of healthy women. Female volunteers were recruited for 2-weeks Pilates intervention. Blood has been collected and anthropometric parameters were measured before and after exercise period (EP). Plasma insulin, cortisol, and dehydroepiandrosterone sulphate levels, erythrocyte antioxidant activity, glutathione levels, NK cytotoxicity and plasma cytokines were analysed. We found a decrease in erythrocyte antioxidant enzymes SOD and GPx activity; GSH levels; in the pro-inflammatory chemokine MCP-1 and trend to reduction in MIP-1β, PDGF and VEGF levels in plasma. NK cell cytotoxic activity increased after Pilates EP in the percentage of specific lysis at 25:1 effector: target (E:T) ratio and the same trend was observed at all E:T ratios as well as in the amount of lytic units per 107 cells. Our findings show that Pilates exercise may improve NK cell immune response and inflammatory milieu in plasma of healthy women.

The Effect of Chitosan on the Erythrocyte Antioxidant Potential of Lead Toxicity-Induced Rats.

In the present study, the effects of chitosan on erythrocyte malondialdehyde (MDA) and glutathione (GSH) levels and glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH) enzyme activities in lead toxicity-induced rats were investigated. Twenty-eight male Wistar albino rats were divided into four groups of control (C), lead group (Pb group), lead+chitosan group (Pb+CS group), and chitosan group (CS group). Lead groups were administered 50mg/kg lead acetate intraperitoneally (ip) for 5days and chitosan groups were administered 200mg/kg chitosan for 28days via gavage. At the end of the study, lead levels were measured in the blood; MDA and GSH levels and GPx, GR, and G6PDH activities were measured in the erythrocyte. It was determined that, in parallel with the increase of full blood lead levels in the Pb group, erythrocyte MDA levels increased significantly, while GSH levels and GSH-Px, GR, and G6PDH activities decreased when compared to those in the C and CS groups (p˂0.05). There was a statistically significant decrease in lead and MDA levels and GSH level and GSH-Px activity increased (p˂0.05) in the Pb+CS group, where chitosan was administered as a protective agent in addition to lead, when compared to the Pb group. There were no differences between the Pb+CS group and the other three groups based on GR and G6PDH activities (p˃0.05). No statistically significant difference was found between the C and CS groups based on the parameters of analysis (p˃0.05). The findings of the present study demonstrated that lead increased oxidative stress by increasing free radical production in erythrocytes, and chitosan was effective in removing the lead from the circulation and enforced the antioxidant defense system.

Erythrocyte glutathione levels as long-term predictor of transition to psychosis

A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion ‘low erythrocyte GSH’ to the set of criteria used to identify individuals at risk of psychosis may be indicated.