Changes In Glutathione Peroxidase Activity Research Articles

Effects of Epigallocatechin Gallate on the Cytotoxicity of Epirubicin-HCl in Lung Cancer Cells

Background: Studies have shown that epigallocatechin-3-gallate (EGCG), which is present in green tea at a higher rate than other components, has an additive or synergistic cytotoxic effect when applied with different anticancer drugs and reduces the side effects caused by anticancer drugs. It is known that the order of administration of drugs in combined applications also affects cytotoxicity. In this context, in our study, the most effective application sequence was determined by evaluating the cytotoxic responses of epirubicin-HCl and EGCG according to the different application order in A-549 cells (NSCLC). Methods: To demonstrate the apoptotic activity, we detected changes in mRNA ratios of Bax, a pro-apoptotic gene, and Bcl-2, an anti-apoptotic gene, (Bax/Bcl2), as well as changes in the activity of caspase 3/7 enzyme. To demonstrate the effect of oxidative stress generation, we investigated changes in glutathione peroxidase activity. Results: It was observed that the cell viability of A-549 cells exposed to different concentrations of epirubicin-HCl and EGCG for 48 h decreased depending on the concentration increase. According to the results of cell viability in cells to which epirubicin-HCl (<IC50) and EGCG (<IC50) were treated with together, and the combination index (CI) value calculations, the most effective combination concentrations were determined to be IC20 Epirubicin-HCl and IC10 EGCG. LDH activities were found higher in epirubicin-HCl + EGCG treatment than epirubicin-HCl alone treatment compared to control groups. Treatment of epirubicin-HCl with EGCG was found to be more effective in increasing glutathione peroxidase activity than epirubicin-HCl alone. Both of epirubicin-HCl alone and combination traetments caused increase in Bax/Bcl-2 ratio in A-549 cells. Conclusion: Combination therapy of epirubicin-HCl with EGCG may be a light in the future for lung cancer patients who are tried to be treated with conventional chemotherapy drugs but cannot achieve the desired success.

Natural high ambient temperature-induced respiratory hypocapnia without activation of the hypothalamic-pituitary-adrenal axis in lactating goats.

Activation of breathing, the hypothalamic-pituitary-adrenal (HPA) axis, and plasma antioxidant defense are adaptive mechanisms in lactating dairy goats fed during the summer season. However, an excess of these responses can interfere with the gas exchange. This study aimed to investigate the effect of natural high ambient temperature (HTa) on blood gas parameters and their relation to the HPA axis and antioxidant defense. Six mid-lactating goats were included in this study and were fed in individual pens for 2 weeks. The data on ambient conditions, physiological responses, and blood chemistry were measured for two sampling days (D7 and D14), 1 week apart during the late summer season. On this two-sampling day, the main physiological responses to HTa, including respiration rate (RR), rectal temperature (Tr), blood gas, and blood chemistry, were measured in the morning and afternoon. Goats from both D7 and D14 increased RR and Tr significantly according to morning and afternoon periods. In addition, goats were at the hypocapnia stage during afternoon panting without a change in blood pH and bicarbonate levels. Interestingly, HTa-induced hypocapnia was not accompanied by an increase in plasma cortisol levels. Finally, ΔTa was negatively correlated with changes in glutathione peroxidase activity. The natural HTa (ΔTa; 5-8°C) in this study activated evaporative heat dissipation and was high enough to induce respiratory hypocapnia. Importantly, this ΔTa did not activate the HPA axis but was correlated with a change in antioxidant defense. Therefore, under natural HTa in tropical conditions, respiratory hypocapnia is the first line of physiological response in goats within a specific range of natural ΔTa (5-8°C).

In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells.

JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as "spice," "herbal incense," or "herbal blend," as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug's toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150μM JWH-018 over 24h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P<0.05. JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

DNA damage in kidney and parenchymal and non-parenchymal liver cells of adult Wistar rats after subchronic oral treatment with tembotrione.

DNA damage in the liver and kidney cells of adult male Wistar rats was studied using the comet assay after a 28-day oral administration of tembotrione at doses of 0.0007, 0.0013 and 0.7 mg/kg b.w./day [AOEL (acceptable operator exposure level), REL (residual exposure level) and 1000× AOEL]. As a descriptor of DNA damage, tail intensity was used. Antioxidant status was assessed by activity of glutathione peroxidase (GPx). Significant DNA damage was recorded in the kidney cells at all three doses as compared to negative control. In parenchymal liver cells, significant DNA damage was observed in AOEL and 1000× AOEL doses, while in non-parenchymal liver cells, only AOEL-treated group was significantly different compared to negative control. In both types of liver cells, REL and 1000× AOEL doses were significantly different from the AOEL dose. No significant changes in GPx activity compared to control were observed at any exposure level. The results of the present study suggest that repeated in vivo exposure to tembotrione led to low-level DNA instability in kidney and liver cells. Exposure to the highest tembotrione dose showed a relatively weak response with the alkaline comet assay. Further research should focus on the effects of this herbicide in other models along with different exposure scenarios.

P2499Effects of aerobic and resistance exercise on skeletal muscle of infarcted rats

Abstract Background Skeletal muscle changes contribute to reduced physical performance after myocardial infarction (MI). Exercise has been recommended to stable patients. However, the effects of resistance exercise after MI are not clear. We compared the effects of aerobic and resistance exercise initiated during compensated cardiac remodeling in infarcted rat gastrocnemius muscle. Methods Three months after MI induction, Wistar rats were divided into four groups: Sham (n=20); sedentary MI (MI-S, n=9); aerobic exercised MI (MI-A, n=9); and resistance exercised MI (MI-R, n=13). Exercised rats trained three times a week for 12 weeks on a treadmill or ladder. Energy metabolism, oxidative stress markers, and antioxidant enzyme activities were assessed by spectrophotometry. Satellite cells activation markers (MyoD, NCAM, and myosin heavy chain neonatal isoform) were assessed by immunofluorescence or Western blot (Pax-7). Statistical analysis: ANOVA or Mann Whitney. Results Physical aerobic capacity was greater in MI-A and strength gain higher in MI-R. Cardiac structures and left ventricular function evaluated by echocardiogram did not differ between infarcted groups. Histological analysis showed that MI size and gastrocnemius cross sectional area did not differ between infarcted groups. Oxygen reactive species production was higher in MI-S than Sham and lipid hydroperoxide concentration was lower in MI-A than the other groups. Catalase activity was higher and glutathione peroxidase lower in infarcted groups than Sham. Superoxide dismutase activity was higher in Sham and MI-R than MI-S. Skeletal muscle metabolism enzyme activity did not differ between groups, except for increase pyruvate kinase in MI-S against the other groups, and β-hydroxyacyl CoA dehydrogenase in MI-S against Sham. Satellite cell activation and protein expression of MAPK and NF-kB did not differ between groups. Conclusion Aerobic and resistance exercise respectively improves physical capacity and muscle strength without changing echocardiographic parameters of infarcted rats. Myocardial infarction increases oxygen reactive species production and changes antioxidant enzyme activity and glucose and fatty acid metabolism. Aerobic exercise is superior to resistance exercise against oxidative stress reducing muscle lipid hydroperoxide concentration and attenuating change in glutathione peroxidase activity. Acknowledgement/Funding Financial support: Fapesp, CNPq, Capes, and UNESP

Changes in Lipase and Antioxidant Enzyme Activities during Processing of Cantonese Sausage with D-Sodium Erythorbate

Pork was used as raw material to produce Cantonese sausage, with additions of 0.05% or 0.1% D-sodium erythorbate. The oxidation indices (peroxide value, TBARS value, carbonyl value, and conjugated dienes value) and enzyme activity (total phospholipase, acid lipase, neutral lipase, superoxide dismutase, and glutathione peroxidase) were measured in the sausages at different processing periods. The results showed slowed lipid oxidation in the presence of D-sodium erythorbate, inhibition of total phospholipase, acid lipase, and neutral lipase activities, and increased superoxide dismutase activity, with little change in glutathione peroxidase activities. When increasing D-sodium erythorbate, the superoxide dismutase activity was negatively correlated with the peroxide value at 5 h (P&lt;0.01), the neutral lipase activity was positively correlated with the conjugated dienes value at 15 h (P&lt;0.01), and the total phospholipase activity was positively correlated with the peroxide value at 30 h (P&lt;0.01). This study explored the antioxidant effect of D-sodium erythorbate and provides a theoretical foundation to improve the quality of Cantonese sausage.

Antiproliferative Effect of Elastin-Derived Peptide VGVAPG on SH-SY5Y Neuroblastoma Cells

Throughout the lifetime of humans, the amount of stem cells and the rate of cell proliferation continue to decrease. Reactive oxygen species (ROS) are one among the many factors that promote stem cell aging. Both a decrease in the level of stem cells and increase in ROS production can lead to the development of different neurodegenerative diseases. This study was conducted to determine how the VGVAPG peptide, liberated from elastin during the aging process and under pathological conditions, affects ROS production and activities of antioxidant enzymes in undifferentiated, proliferating SH-SY5Y cells. SH-SY5Y cells were maintained in Dulbecco’s modified Eagle’s medium/nutrient mixture F-12 supplemented with 10% heat-inactivated fetal bovine serum (FBS). After treating the SH-SY5Y cells with VGVAPG peptide, we measured ROS production; cell metabolism, proliferation, and expression; and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). We demonstrated that the VGVAPG peptide increases GPx expression and activity, whereas it decreases CAT expression in SH-SY5Y cells. Silencing of the GLB1 gene prevents changes in GPx activity. Despite the fact that the VGVAPG peptide increases GPx expression, it increases the ROS level. Moreover, the VGVAPG peptide decreases SH-SY5Y proliferation, which is prevented by the ROS scavenger N-acetyl-L-cysteine. Our data suggest that ROS production and decreased proliferation of SH-SY5Y cells are the results of excitotoxicity meditated through close unrecognized molecular pathways. More research is needed to elucidate the unknown mechanism of action of VGVAPG peptide in the nervous system.

RENO-PROTECTIVE EFFICACY OF AQUEOUS CINNAMON BURMANNI EXTRACT ON MULTI-WALLED CARBON NANOTUBES-INDUCED TOXICITY

Multi-walled carbon nanotubes (MWCNTs) are widely used in industrial and biomedical applications. Exposure to these tubes causes inflammation, oxidative stress and/or function disorders in the body tissues and systems. The use of certain natural products that have antioxidant and/or anti-inflammatory activities might decrease this toxicity. Thus, the present study aims to assess the four weeks toxicity effect of inhaled MWCNTS on the kidneys of male rats, and the possible protective effect of aqueous extract of Cinnamon Burmanni (C. Burmanni). MWCNTs were synthesized in nano-photonic lab (Faculty of Science, Beni-Suef University). Thirty-two male rats (Rattus norvegicus) were divided equally into 4 groups: control group, cinnamon-treated group (daily, orally administrated 75 mg/kg body weight of aqueous C. Burmanni extract for 4 consecutive weeks), MWCNTs-treated group (animals were subjected to wood shaving cage litter containing 1.0 g MWCNTs/kg body weight, twice a week), and cinnamon and MWCNTs-treated group (treated simultaneously with both MWCNTs and aqueous C. Burmanni extract). Estimation of nitrite content, total thiols and reduced glutathione (GSH) concentrations, as well as glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities in serum, in addition to the histopathological examination of kidney sections, were carried out. MWCNTs exposure resulted in significant elevation of nitrite content with significant decrease in GSH and total thiols levels and GST activity, and non-significant change in GPx activity in the serum samples. Histopathological studies of MWCNTs inhaled rats showed proteinaceous material accumulation in the lumen of renal tubules, vacuolation and congestion of glomerular tufts and perivascular oedema. Aqueous C. Burmanni extract greatly ameliorated these lesions via a significant decrease in serum nitrite content and significant elevation of serum GSH and total thiols contents as well as GST and GPx activity compared to their respective controls. In conclusion, aqueous C. Burmanni extract showed reno-protective effect against MWCNTs-induced cytoxicity via lowering reactive nitrogen species level and alleviating antioxidant enzymatic and non-enzymatic markers.

Expression of P-Glycoprotein in the Blood-Brain Barrier and Its Interaction with Redox State in Cerebral Ischemia and Ischemia-Reperfusion

Studies on Wistar rats addressed P-glycoprotein expression in the blood-brain barrier in conditions of unilateral occlusion and occlusion-reperfusion of the common carotid artery. The interaction between expression of the transporter protein and measures of free radical status in cerebral cortex tissues in these conditions was assessed. Unilateral occlusion of the common carotid artery in rats was found to lead to a decrease in P-glycoprotein expression in the blood-brain barrier of the frontal lobe of the cerebral cortex at 12 h, with an increase in expression by day 5 of the experiment. Unilateral occlusion of the common carotid artery for 30 min with subsequent reperfusion decreased transporter expression at 4 and 12 h after reperfusion. The dynamics of P-glycoprotein expression correlated with changes in glutathione peroxidase activity in brain tissue.

Glutathione content in sperm cells of infertile men

Hyperproduction of reactive oxygen species can damage sperm cells and is considered to be one of the mechanisms of male infertility. Cell protection from the damaging effects of free radicals and lipid peroxidation products is generally determined by the degree of antioxidant protection. Glutathione is non-enzymatic antioxidant which plays an important protective role against oxidative damages and lipid peroxidation. The aim of the present work is to determine the content of reduced and oxidized glutathione in sperm cells of infertile men. Semen samples from 20 fertile men (normozoospermics) and 72 infertile patients (12 oligozoospermics, 17 asthenozoospermics, 10 oligoasthenozoosper­mics and 33 leucocytospermic) were used. The total, oxidized (GSSG) and reduced (GSH) glutathione levels were measured spectrophotometrically. The levels of total glutathione were significantly lower in the spermatozoa of patients with oligozoo-, asthenozoo- and oligoasthenozoospermia than in the control. Infertile groups showed significantly decreased values of reduced glutathione in sperm cells vs. fertile men, indicating an alteration of oxidative status. The oxidized glutathione levels in sperm cells of infertile men did not differ from those of normozoospermic men with proven fertility. The GSH/GSSG ratio was significantly decreased in the oligo-, astheno- and oligoasthenozoospermic groups compared to the normozoospermic group. In patients with leucocytospermia the GSH/GSSG ratio was lower but these changes were not significant. In addition, glutathione peroxidase activity in sperm cells was decreased in patients with oligozoo-, astenozoo-, oligoastenozoospermia and with leucocytospermia. The most significant changes in glutathione peroxidase activity were observed in infertile men with leucocytospermia. Decreased GSH/GSSG ratio indicates a decline in redox-potential of the glutathione system in sperm cells of men with decreased fertilizing potential. Redistribution between oxidized and reduced forms of glutathione can be caused by depletion of intracellular stores of glutathione and intensification of lipid peroxidation processes. This leads to increased production of reactive oxygen species, further depletion of antioxidant pools and disturbances of structure and function of spermatozoa. Our results indicate that the evaluation of reduced glutathione level and GSH/GSSG ratio in sperm cells of infertile men can be helpful in fertility assessment.

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BackgroundDiabetes is the western world’s leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease.Research design and methodsWe have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1–3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of—and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine).Expected resultsThe study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups.ConclusionsOutcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress.Trial registration ISRCTN 97358113. Registered 21st September 2009

Evaluation of lipid peroxidation and antioxidant status on fenvalerate, nitrate and their co-exposure in Bubalus bubalis

The toxic effects of pesticides and minerals have been explored in different species, but still there is paucity of information regarding their combined toxicological effects. The present investigation reports oxidative stress induced by oral subacute exposure to fenvalerate (1 mg/kg) and sodium nitrate (20 mg/kg) alone, as well as in combination daily for 21 days in buffalo calves. Fenvalerate exposure produced significant elevation in lipid peroxidation (LPO), glutathione peroxidase (GPx), while it produced significant decline in blood glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT). No significant alteration was evidenced in nitric oxide (NOx) levels. Oral exposure to sodium nitrate produced significant inclination in LPO and NOx, while on the other hand significant depreciation in SOD and CAT with no significant change in GPx activity. Combined exposure to fenvalerate and sodium nitrate produced severe effects with an appreciably more prominent elevation in extent of LPO and decline in blood GSH levels.

Increased oxidative stress and decreased membrane fluidity in erythrocytes of CAD patients

One of many risk factors for cardiovascular disease appears to be oxidative stress. To estimate possible changes in redox balance, membrane fluidity, and cholesterol level in erythrocytes was collected erythrocytes from patients diagnosed with coronary artery disease (CAD). The study included 20 patients with previous myocardial infarction occurring more than 6 months prior to the time of screening with low-density lipoprotein cholesterol (LDL-C) > 70 mg/dL and 21 healthy controls. The following parameters were studied: catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), thiobarbituric acid reactive substrates (TBARS), sulfhydryl (SH) groups in membrane protein, total cholesterol level, and erythrocyte membrane fluidity. Our study showed an increase in the level of lipid peroxidation (13%) and total cholesterol (19%), and a decrease in membrane fluidity (14%) in the subsurface layers and in the deeper layers of erythrocyte membrane (7%) isolated from patients with CAD in comparison to healthy controls. A significant decrease in catalase (10%) and SOD (17%) activities were also observed. No changes in GPx activity or the level of SH groups were observed. Our study indicates that there are disorders in the antioxidant system as well as changes in the membrane structure of erythrocytes obtained from CAD patients.

Abstract 1997: Resveratrol modifies the activity and expression of antioxidant enzymes in somatic cancer cells

Abstract Background &amp; Objectives: Resveratrol has been reported as a potent anti-cancer compound, but it's mode of action is not completely understood. In this study, we investigated the effects of resveratrol treatment on the activity and expression of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in three somatic cancer cell lines: PC-3 (prostate cancer), MCF-7 (breast cancer) and HepG2 (hepatocellular cancer). Methods: The cells were treated with different concentration (0-200 μM) of resveratrol for 24, 48 and 72 hours.Cell growth was studied by cell counting; cell homogenate was taken for the measurement of enzyme activities; proteins were isolated for western blotting to measure the genetic expression. Results: Resveratrol showed dose-dependent growth inhibitory activity in all cells. It was significantly effective against PC-3 and HepG2 even in 10 μM, and 25 μM concentration, but not in MCF-7 cells. However 50 μM showed significant growth inhibitory effect in MCF-7, and also in HEK293T (human embryonic kidney cell line as control) cells. 25 μM was identified as most effective dosage against PC-3 and HepG2 cells, without affecting HEK293T cells. Treatment of 25 μM for 48 hours increased the activity of SOD enzymes by 3-4 folds in PC-3; 2-3 folds in HepG2; 1.5-1.8 folds in MCF-7; and 1.2-1.5 folds in HEK293T cells. Resveratrol treatment also significantly increased the activity of CAT in HepG2, moderately in MCF-7, but non-significantly in PC-3 and HEK293T cells. However, the treatment of resveratrol showed no significant change in GPX activity in any cell line. Western blotting also revealed the increased expression of SOD2 in PC-3, and HepG2 cells at 25 μM resveratrol treatment. CAT expression was moderate, but no change in GPX1 expression was found in the tested cancer cells. Conclusions: The results of this study could confirm the dose dependent growth inhibitory potential of resveratrol; however, the dose of resveratrol in treatment of the cancer cells should be limited, as higher dose (Δ50 μM) has also been found dangerous for normal cells (HEK293T). Resveratrol at low dose (25 μM) potentially increases the activity and expression of SOD enzyme in cancer cells while inhibiting cell growth. Moderate increase of CAT activity and expression is also observed, but no significant change in GPX activity and expression in cell lines used in this study. These findings may contribute to understanding the mechanisms of resveratrol action in treatment of cancer. The work was supported by the National Basic Research Program of China (No. 2011CB910700-704) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1997. doi:1538-7445.AM2012-1997

Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains

Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40mg/kg per day, for the 3%Co–0.04%Ca and 6%Co–0.08%Ca treatments, respectively. At 90days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive function.

Acute Phase Response of Selenium Status and Glutathione Peroxidase Activity in Blood Plasma Before and After Total Knee Arthroplasty Surgery

Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p < 0.05) and decreases in the plasma Se concentration (p < 0.05) and in serum albumin (p < 0.05) after surgery were observed. Since albumin is a Se-containing protein and represents a negative acute phase protein that provides amino acids for the production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.

Cd/Se/Te-based quantum dot 705 modulated redox homeostasis with hepatotoxicity in mice

The objective of this study was to investigate whether quantum dot 705 (QD705) disrupts the cellular antioxidant systems leading to hepatotoxicity in mice. Mice were intravenously injected with QD705 and then sacrificed at week 12 or 16. Homeostasis of antioxidant-related metals, antioxidant activities, induction of oxidative stress, and toxicity in the liver were investigated. Although no histopathological change was observed, a time- and dose-dependent increase in metallothionein expression and reduction in liver function was noticed. Increased copper, zinc, and selenium levels and enhancements of the trace metal-corresponding transporters were noted at week 12. At week 16, a decline of selenium from its elevated level at week 12 was observed, which was accompanied by changes in glutathione peroxidase activity as well as in redox status. A significant reduction in superoxide dismutase activity was observed at 16 weeks. Furthermore, a corresponding elevation of heme oxygenase-1 expression, 8-oxo-7,8-dihydro-2′-deoxyguanosine, interleukin-6 and tumor necrosis factor-alpha suggested the presence of oxidative stress, oxidative DNA damage and inflammation.

Effects of excessive selenium supplementation to diet contaminated with deoxynivalenol on blood phagocytic activity and antioxidative status of broilers

This study examined the effects of excessive dietary supplementation with organic selenium on phagocytic activity and antioxidative status of chickens for fattening fed diet contaminated with deoxynivalenol (DON). Sixty chickens of Ross 308 hybrids were at day of hatching divided into four groups with 15 birds in each. The background DON dietary levels in both negative and positive control groups were 0.2 mg/kg. The complete feed for positive control group was supplemented with Se dose 1 mg/kg in the form of Se-yeast. Group 3 was fed diet with DON level 3 mg/kg while diet for group 4 combined DON level 3 mg/kg with a excessive supplement of Se-yeast (Se dose 1 mg/kg). After 6 weeks of dietary intake, six randomly-chosen chickens from each group were sampled. Feeding of contaminated diet resulted in significantly reduced blood phagocytic activity (19.5 ± 1.1% in the negative control vs. 12.8 ± 0.8% in the DON-treated group, p < 0.05). Se-yeast supplemented to the DON contaminated diet prevented suppression of phagocytic activity. Dietary intake of DON at levels 3 mg/kg did not influence the plasma α-tocopherol level while excessive dietary Se dose reduced it in both Se supplemented groups. Neither the birds of DON-treated group nor the birds from group 4 with DON and Se-yeast showed any response in plasma γ-glutamyltransferase (GGT) activity. Subtoxic dietary level of DON significantly increased the activity of glutathione peroxidase (GPx) in the duodenal mucosa, while additional Se supplementation prevented such a response to mycotoxin. On the other hand, both Se supplemented groups showed significantly elevated GPx activities in blood, liver and kidney, (p < 0.05). The results suggest a potential ability of excessive supplementation of organic selenium to prevent the blood phagocytic activity suppression and changes in GPx activity in duodenal tissue induced in broilers by subtoxic dietary levels of DON.

Dysregulated glutathione metabolism links to impaired insulin action in adipocytes

Oxidative stress plays an important role in obesity-related metabolic diseases. Glutathione peroxidase (GPX) is an antioxidant enzyme downregulated in adipose tissue of obese mice. However, the role of GPX in adipocytes remains elusive. The objective of this study was to clarify the pathophysiological changes in GPX activity and glutathione metabolism and their roles in the pathogenesis of insulin resistance in adipocytes. To achieve this goal, we measured cellular GPX activity, glutathione (GSH) contents, GSH/GSSG ratio, and mRNA expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for de novo GSH synthesis, in adipose tissue of control and ob/ob mice and in 3T3-L1 adipocytes treated with insulin, H(2)O(2), free fatty acid (FFA), or TNFalpha. Furthermore, we investigated the effects of GPX inhibition with a specific GPX inhibitor or RNA interference against GPX, H(2)O(2), and reduced GSH on insulin signaling in 3T3-L1 adipocytes. ob/ob Mice showed not only a decrease in cellular activity of GPXs (GPX1, -4, and -7) but also an increase in gamma-GCS expression, resulting in increased GSH contents in adipose tissue. These alterations in glutathione metabolism were also observed during differentiation of 3T3-L1 cells and their exposure to insulin, FFA, or H(2)O(2). Inhibition of GPX activity, addition of GSH, and H(2)O(2) resulted in impaired insulin signaling in 3T3-L1 adipocytes. These results suggest that decreased GPX activity and increased gamma-GCS expression lead to overaccumulation of GSH, which might be involved in the pathogenesis of insulin resistance in obesity.

Effets chroniques de faibles doses de carbonate de lithium chez la souris. Relations entre statut oxydant et modifications fonctionnelles et structurales des reins et du cerveau

Effects of daily injections of lithium carbonate (20, 40 or 80 mg/kg body weight) during 14 and 28 days were investigated in Wistar mice. Attention was paid (1) to changes in concentrations of lithium, creatinine and urea in serum, (2) to level of oxidative stress by measuring lipids peroxidation level and catalase, superoxide-dismutase and glutathione-peroxidase activities, and (3) to changes in the histological structure of brain. The first intraperitoneal injection was followed by a transitory peak of lithium in the blood, reaching 0.25 mM and 1.1 mM and disappearing 6 and 12 h later for the 20 and 80 mg/kg doses, respectively. From the first to the last day of treatment, lithium concentrations in the blood, measured 12 h after the injections, increased from 0 to 0.11 mM (20 mg/kg dose) or 0.25 mM (80 mg/kg dose). The 80 mg/kg treatment induced a renal insufficiency evidenced by an increase of blood creatinine and urea levels. Lithium treatment was found to trigger an oxidative stress in kidney, but not in brain. In kidney, the lipid peroxidation level (TBARS) and the superoxide dismutase and catalase activities were increased. No change in glutathione peroxidase activity was detected. Histology of the brain cortex revealed interesting modifications: thicker neuronal cells and a denser network of dendrites, as compared to controls. To cite this article: R. Nciri et al., C. R. Biologies 331 (2008).