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Glutathione Levels (glutathione + level)
Kinds of Glutathione Levels Selected AbstractsEradication of Helicobacter pylori Restores Glutathione S-Transferase Activity and Glutathione Levels in Antral MucosaCANCER SCIENCE, Issue 12 2001Arnoud H. A. M. van Oijen Glutathione S-transferases (GST) and glutathione peroxidases (GPO) are important in detoxification. GST activity in the mucosa of the gastrointestinal tract is inversely correlated with the development of gastrointestinal cancer. Helicobacter pylori (H. pylori) infection has been associated with gastric cancer. We studied GST activity and the substrate glutathione (GSH) in patients with H. pylori-associated gastritis. GST activity and isoenzyme levels, GPO activity and GSH levels were studied in antral biopsies of 38 H./pyfori-positive patients, before and after eradication treatment. In 31 patients in whom H. pylori was successfully eradicated, antral GST enzyme activity before therapy was 532 (465,598) nmol/mg protein-min (mean and 95% confidence interval) and that after therapy was 759 (682,836) nmol/mg protein-min (P<0.0001). Correspondingly, levels of GST , and GST-P1 were higher after eradication (P<0.001). GSH concentration significantly increased: 21.2 (16.2,26.2) nmol/mg protein before and 27.1 (23.6,30.6) nmol/mg protein after therapy (P<0.05). In 7 patients in whom H. pylori was not eradicated, GST activity was 671 (520,823) nmol/mg protein min and 599 (348,850) nmol/mg protein before and after treatment respectively (P=0.32). GSH levels were 17.4 (9.0,25.7) nmol/mg protein and 18.2 (9.1,27.3) nmol/mg protein, respectively (P=0.84). No differences in antral GPO enzyme activity, both of selenium (Se)-dependent and total GPO, before and after successful treatment were found. Eradication of H. pylori infection increases GST activity and GSH levels in antral mucosa. Low GST activity and GSH concentration due to H. pylori infection might play a role in gastric carcinogenesis. [source] Structural changes, chemical composition and antioxidant activity of cherry tomato fruits (cv. Micro-Tom) stored under optimal and chilling conditionsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2009Perla Gómez Abstract BACKGROUND: Cherry tomato fruits cv. Micro-Tom, a model plant for tomato genetics, were analysed in order to determine the main structural and chemical changes under optimal and chilling storage conditions. The comparison of Micro-Tom to standard tomato cultivars will give an insight into suitability of this dwarf cultivar as a model for studying the influence of low-temperature conditions on tomato fruits. RESULTS: During chilling, fruit tissue was progressively destroyed due to the collapse of the deep layers of the pericarp. Chilling lowered the typical tomato kinetics of ripening in sugars (glucose, fructose, sucrose), organic acids (tartaric, malic, citric, ascorbic and succinic) and the antioxidants phenol and lycopene, while carotenoid synthesis seemed to be blocked. Glutathione level was elevated and the activity of ROS scavenging enzymes was altered. Essentially, Micro-Tom fruits showed a quality evolution that was similar to that described for standard tomato cultivars. CONCLUSION: The cherry tomato cultivar Micro-Tom could be used as a model for studying the influence of low temperature on biochemical and structural changes taking place during chilling injury conditions. Copyright © 2009 Society of Chemical Industry [source] Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of miceJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2001R. Jagannathan Abstract Pyridostigmine bromide (PB), a reversible anticholinesterase drug, had been used against possible nerve gas exposure during the Persian Gulf War. The Gulf War veterans used PB and they were under physical stress. This study investigated the delayed and interactive effects of pyridostigmine and physical stress on the antioxidant defense system in triceps muscle of mice. Male NIH Swiss mice were divided into four groups and treated as follows: sedentary control; pyridostigmine (1.2 mg kg,1 p.o.); exercise; and PB plus exercise. Mice were exercised for 10 weeks, but PB was administered daily during the 5th and 6th weeks. Mice were sacrificed 24 h after the last treatments and the triceps muscle was isolated and analyzed. There was a significant increase in total superoxide dismutase (CuZn-SOD + Mn-SOD) activity (141% of control) with PB plus exercise, suggesting that any influx of superoxide anions was scavenged efficiently. The Mn-SOD enzyme protein levels were reduced significantly (63% of control) by PB plus exercise. Catalase enzyme protein levels were increased significantly by exercise (132% of control) as well as by PB plus exercise (139% of control). Glutathione levels were increased significantly by exercise alone (123% of control). Pyridostigmine bromide plus exercise significantly increased the malondialdehyde concentration (124% of control) in the triceps muscle, indicating an oxidative stress response of the combination. The data indicate that a combination of PB ingestion and exercise training significantly altered the antioxidant enzyme activities, enzyme protein levels and lipid peroxidation, leading to oxidative injury. Physical stress amplified the delayed effects of PB in the skeletal muscle of mice. Copyright © 2001 John Wiley & Sons, Ltd. [source] Epigallocatechin gallate attenuates experimental non-alcoholic steatohepatitis induced by high fat dietJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8pt2 2008Nalan Kuzu Abstract Background and Aim:, In the present study, we examined the preventive role of epigallocatechin gallate (EGCG) in an experimental non-alcoholic steatohepatitis model induced by a high fat diet. Methods:, The study included 21 male Sprague-Dawley rats, which were equally divided into three groups. The first group was fed on a standard rat diet, the second group on a high fat diet (HFD), and the third group on a HFD + EGCG. The study concluded after 6 weeks. Histopathological examination was performed. Plasma and tissue MDA levels, glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, triglyceride, and cholesterol levels were studied. Insulin resistance was calculated by the homeostasis model of insulin resistance method. Results:, Steatosis, inflammation, ballooning degeneration, and necrosis increased significantly in the HFD group, compared to the control group (P < 0.01). Steatosis and inflammation decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.05, for each). There was a significant decline in ALT (P < 0.01), triglyceride (P < 0.01), insulin (P < 0.05), and glucose (P < 0.05) levels in the HFD + EGCG group, when compared to the HFD group. Plasma and liver MDA levels in the HFD + EGCG group were lower than those of the HFD group; the difference was significant (P < 0.01 for each). Glutathione levels in the HFD + EGCG group was significantly higher those in the HFD group. CYP 2E1 and ,-smooth muscle actin expression decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.01, P < 0.05, respectively). Conclusion:, EGCG reduces the development of experimental non-alcoholic steatohepatitis induced by a high fat diet. It seems to exercise this effect through its effect on lipid metabolism and antioxidant characteristics. [source] SHORT COMMUNICATION: Increased Expression of Glutathione by Estradiol, Tumor Necrosis Factor-Alpha, and Interleukin 1-Beta in Endometrial Stromal CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Sa Ra Lee Problem, The intracellular antioxidant system, based on glutathione (GSH), plays a key role in endometrial detoxification reactions and has been proposed to be involved in the pathogenesis endometriosis. This study was designed to evaluate whether estradiol (E2) and proinflammatory cytokines have any effects on expression of glutathione in endometrial stromal cells (ESCs). Method of study, Glutathione levels were measured utilizing high-performance liquid chromatography following in vitro culture and treatment of ESCs with estradiol, tumor necrosis factor-alpha (TNF-,) and interleukin 1-beta (IL-1,). Results, The GSH level in E2 (10,8 m) treatment group was significantly higher than in the control group at 48 h (P < 0.05). In vitro treatment of ESCs with TNF-, 10 ng/mL as well as E2 (10,8 m) plus TNF-, 10 ng/mL for 48 hr also led to a significant increase in GSH level (P < 0.05; P < 0.05, respectively). Both IL-1, 10 ng/mL and E2 (10,8 m) plus IL-1, 10 ng/mL for 48 hr increased GSH level significantly (P < 0.05; P < 0.05, respectively) as well. Conclusions, These findings might suggest that increased production of estradiol and proinflammatory cytokines in the peritoneal cavity possibly leads to the establishment of endometriosis through increased level of GSH. [source] Acute effects of the sigma-2 receptor agonist siramesine on lens epithelial cellsACTA OPHTHALMOLOGICA, Issue 2007JO KARLSSON Purpose: Experiments were carried out to study the effects of siramesine on markers for apoptosis, oxidative damage and mitochondrial function in primary cultures of human lens epithelial cells (HLEC). Methods: HLEC were incubated with 25 ,M siramesine for 1, 2, 3, 4, 6 and 8 hours. Caspase-3 was assayed in cell extracts with DEVD-AMC. Mitochondrial depolarization was assayed with JC-1. Peroxide production was studied with DCF-DA and superoxide levels with hydroethidium. Glutathione levels were assayed with monochlorobimane. Results: Siramesine induced a significant increase of caspase-3 activity after 6h exposure to 25 ,M siramesine. Nuclear morphology examined with Hoechst 33342 showed signs of apoptosis after the same time intervals. A significant increase in the production of peroxide and superoxide were found up to 4 -8 hours after administration of siramesine. Conclusions: Siramesine, a piperidine analogue, was developed for the treatment of psychiatric disorders and is considered to be relatively nontoxic. This study, and others, indicate effects on cell growth, apoptosis and production of ROS. The sigma-2 receptor may be a regulator of HLEC growth and apoptosis. [source] Changes in oxidative balance in rat pericytes exposed to diabetic conditionsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004A. Manea Abstract Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2,-7, dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. Athree times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy. [source] ANTIOXIDANT ACTIVITIES AND HYPOLIPIDEMIC EFFECTS OF AN AQUEOUS EXTRACT FROM FLOWER BUDS OF CLEISTOCALYX OPERCULATUS (ROXB.) MERR.JOURNAL OF FOOD BIOCHEMISTRY, Issue 6 2009AND PERRY ABSTRACT The antioxidant activities and hypolipidemic effects of aqueous extract from Cleistocalyx operculatus flower buds (COB) (Roxb.) Merr. and Perry, a commonly used material for drink preparation in Vietnam, were investigated in vitro and in diabetic rats. In vitro, the aqueous extract of COB which has highest phenolic and flavonoid contents showed a strong antioxidant effect and highest pancreatic lipase inhibitory activity when compared with green tea and guava leaf extracts. Oral administration of aqueous extract from COB (500 mg/kg body weight/day) on streptozotocin-induced diabetic rats for 8 weeks resulted in significant reduction in the levels of glucose, total cholesterol and triglyceride in plasma as well as the concentration of glucose and sorbitol in the lens. In addition, COB showed significant recovery in the activities of antioxidant enzymes (superoxide dismutase, glutathione S-transferase) and glutathione level in liver with markedly decrease in the lipid peroxide level in liver and lens of the COB-treated diabetic rats. These results indicated that COB showed antioxidant activities, prevention of sorbitol accumulation in lens and hypolipidemic effects in addition to its antidiabetic effects and may be considered as a promising material for the prevention of diabetic complications and metabolic syndrome. PRACTICAL APPLICATIONS In recent years, research on traditional medicinal plants for the management of diabetes has attracted the interest of medical scientists. A suitable plant material for antidiabetes and prevention of diabetic complications should possess various biological components, such as antihyperglycemia, antioxidant activities and antihyperlipidemia, without side effects. In this study, the aqueous extract from Cleistocalyx operculatus flower buds (COB) with high polyphenolic and flavonoid content has shown beneficial biological functions in vitro and in diabetic rats, including antioxidant activity, hypolipidemic and hypoglycemic effects. The results of our study suggest that COB might have a potential role in the management of the prediabetic state and the prevention of diabetic complications. Therefore, there is the possibility for the development of C. operculatus as a beverage for the prevention of diabetes, as well as the prevention of the metabolic syndrome. [source] Use of L -[15N] glutamic acid and homoglutathione to determine both glutathione synthesis and concentration by gas chromatography-mass spectrometry (GCMS)JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2001Bernard Humbert Abstract A method for simultaneous measurement of both glutathione enrichment and concentration in a biological sample using gas chromatography mass spectrometry is described. The method is based on the preparation of N,S -ethoxycarbonylmethyl ester derivatives of glutathione, and the use of homoglutathione (glutamyl,cysteinyl,alanine) as an internal standard. A procedure for determination of glutamate concentration and enrichment is also reported. Both methods have within-day and day-to-day inter-assay coefficients of variation less than 5%, and recoveries of known added amounts of glutathione and glutamate are close to 100%. Taken together, these methods allowed determination of glutathione concentration and fractional synthesis rate in red blood cells using L -[15N] glutamic acid infusion. This approach was applied in vivo to investigate the effects of a 72 h fast, compared with a control overnight fast, on erythrocyte glutathione in a single dog. The 72 h fast was associated with a 39% decline in erythrocyte glutathione level, (2.9 ± 0.4 versus 4.7 ± 0.5 mmol l,1, fasting versus control) with no change in glutathione fractional synthesis (67.4 versus 71.3% d,1, fasting versus control). Copyright © 2001 John Wiley & Sons, Ltd. [source] The role of erythropoietin in the protection of gastric mucosa from indometacin-induced gastric injury and its relationship with oxidant and antioxidant parameters in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2010Fatih Albayrak Abstract Objectives Erythropoietin has anti-oxidative and anti-inflammatory activity. We wanted to evaluate its activity in preventing damage to the gastric mucosa. Methods We examined the protective effect of erythropoietin on indometacin-induced gastric mucosa damage in the rat stomach and compared its potency with that of famotidine. We also measured effects on oxidant and antioxidant parameters in the rat stomach. Key findings Famotidine and erythropoietin 2500 and 5000 IU/kg reduced the ulcer area by 98%, 31% and 58%, respectively, compared with the indometacin group. Superoxide dismutase activity and glutathione level were decreased and myeloperoxidase activity increased in the indometacin group compared with healthy rats. Famotidine and erythropoietin at all doses increased superoxide dismutase and glutathione levels significantly compared with the indometacin group. Myeloperoxidase activity was decreased by erythropoietin and famotidine. Conclusions These results support the view that erythropoietin counteracts the effects of indometacin in inducing gastric ulcer and could be used as a an antiulcer compound. Its antiulcer effect is less potent than that of famotidine. The antiulcerogenic effects of erythropoietin may be related to its intrinsic ability to sustain the activities of free-radical scavenging enzymes and the bioavailability of glutathione. [source] Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2003Tzung-Yan Lee ABSTRACT Carbon tetrachloride (CCl4) is metabolized by cytochrome P450 to form a reactive trichloromethyl radical that triggers a chain of lipid peroxidation. These changes lead to cell injury, and chronic liver injury leads to excessive deposition of collagen in liver, resulting in liver fibrosis. The aim of this study was to evaluate the effects of long-term Salvia miltiorrhiza administration in CCl4 -induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg,1 twice a day) was given for 9 weeks, beginning at the same time as the injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic glutathione level and an increased glutathione-S-transferase content. The hepatic thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused a prominent collagen deposition in liver histology that was further supported by the increased hepatic mRNA expression of transforming growth factor-,1, tissue inhibitor of metallproteinase-1 and procollagen I. Salvia miltiorrhiza administration led to a dose-dependent increase in hepatic glutathione levels and a decrease in peroxidation products. Additionally, it reduced the mRNA expression of markers for hepatic fibrogenesis. In conclusion, long-term administration of Salvia miltiorrhiza in rats ameliorated the CCl4 -induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis. [source] Evidence that Branch Cuvettes are Reasonable Surrogates for Estimating O3 Effects in Entire Tree CrownsPLANT BIOLOGY, Issue 2 2007C. Then& Abstract: Within the scope of quantifying ozone (O3) effects on forest tree crowns it is still an open question whether cuvette branches of adult trees are reasonable surrogates for O3 responses of entire tree crowns and whether twigs exhibit autonomy in defense metabolism in addition to carbon autonomy. Therefore, cuvette-enclosed branches of mature beech (Fagus sylvatica) trees were compared with branches exposed to the same and different ozone regimes by a free-air fumigation system under natural stand conditions by means of a vice versa experiment. For this purpose, cuvettes receiving 1 × O3 air were mounted in trees exposed to 2 × O3 and cuvettes receiving 2 × O3 air were mounted in trees exposed to 1 × O3 in the upper sun crown. At the end of the fumigation period in September 2004, leaves were examined for differences in gas exchange parameters, pigments, antioxidants, carbohydrates, and stable isotope ratios. No significant differences in foliar gas exchange, total carbohydrates, stable isotope ratios, pigment, and antioxidant contents were found as a consequence of cuvette enclosure (cuvette versus free-air branches) of the same O3 concentrations besides increase of glucose inside the cuvettes and reduction of the de-epoxidation state of the xanthophyll cycle pigments. No significant ozone effect was found for the investigated gas exchange and most biochemical parameters. The total and oxidized glutathione level of the leaves was increased by the 2 × O3 treatment in the cuvette and the free-air branches, but this effect was significant only for the free-air branches. From these results we conclude that cuvette branches are useful surrogates for examining the response of entire tree crowns to elevated O3 and that the defence metabolism of twigs seems to be at least partially autonomous. [source] A predictive high-throughput scale-down model of monoclonal antibody production in CHO cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2009Rachel Legmann Abstract Multi-factorial experimentation is essential in understanding the link between mammalian cell culture conditions and the glycoprotein product of any biomanufacturing process. This understanding is increasingly demanded as bioprocess development is influenced by the Quality by Design paradigm. We have developed a system that allows hundreds of micro-bioreactors to be run in parallel under controlled conditions, enabling factorial experiments of much larger scope than is possible with traditional systems. A high-throughput analytics workflow was also developed using commercially available instruments to obtain product quality information for each cell culture condition. The micro-bioreactor system was tested by executing a factorial experiment varying four process parameters: pH, dissolved oxygen, feed supplement rate, and reduced glutathione level. A total of 180 micro-bioreactors were run for 2 weeks during this DOE experiment to assess this scaled down micro-bioreactor system as a high-throughput tool for process development. Online measurements of pH, dissolved oxygen, and optical density were complemented by offline measurements of glucose, viability, titer, and product quality. Model accuracy was assessed by regressing the micro-bioreactor results with those obtained in conventional 3,L bioreactors. Excellent agreement was observed between the micro-bioreactor and the bench-top bioreactor. The micro-bioreactor results were further analyzed to link parameter manipulations to process outcomes via leverage plots, and to examine the interactions between process parameters. The results show that feed supplement rate has a significant effect (P,<,0.05) on all performance metrics with higher feed rates resulting in greater cell mass and product titer. Culture pH impacted terminal integrated viable cell concentration, titer and intact immunoglobulin G titer, with better results obtained at the lower pH set point. The results demonstrate that a micro-scale system can be an excellent model of larger scale systems, while providing data sets broader and deeper than are available by traditional methods. Biotechnol. Bioeng. 2009; 104: 1107,1120. © 2009 Wiley Periodicals, Inc. [source] Glutathione cycle in stable chronic obstructive pulmonary diseaseCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2010Biljak, Vanja Radi Abstract Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidant/antioxidant imbalance. Glutathione is the most abundant cellular low-molecular weight thiol and the glutathione redox cycle is the fundamental component of the cellular antioxidant defence system. Concentration of total glutathione and catalytic activities of glutathione peroxidase and glutathione reductase were determined in peripheral blood of patients (n,=,109) and healthy subjects (n,=,51). Concentration of total glutathione in patients was not changed in comparison to healthy controls. However, we found statistically significant difference between patients with moderate and severe disease stages. Glutathione reductase activity was increased, while glutathione proxidase activity was decreased in the patients with COPD, when compared to healthy controls. We found no significant difference in glutathione peroxidase and glutathione reductase activities between stages. Patients who smoked had lower concentration of total glutathione compared with former smokers and never-smoking patients. Lung function parameters were inversely associated with glutathione level. Evidence is presented for differential modulation of glutathione peroxidase and glutathione reductase activities in peripheral blood of patients with stable COPD. We suppose that in addition to glutathione biosynthesis, glutathione reductase-dependent regulation of the glutathione redox state is vital for protection against oxidative stress. Copyright © 2010 John Wiley & Sons, Ltd. [source] Protective effects of antioxidant combination against D-galactosamine-induced kidney injury in ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2010Tunc Catal Abstract The protective effects of an antioxidant combination in kidney injury induced by the injection of D-galactosamine (D-GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100,mg,kg,1,day,1), , -carotene (15,mg,kg,1,day,1), , -tocopherol (100,mg,kg,1,day,1), and sodium selenate (0.2,mg,kg,1,day,1) for three days orally, (3) rats injected D-GaIN (500,mg,kg,1) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D-GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D-GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D-GaIN,+,antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D-GaIN-induced kidney injury of rats. Copyright © 2010 John Wiley & Sons, Ltd. [source] 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP),induced mutagenesis in cultured Big BlueÔ rat mammary epithelial and fibroblast cellsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002Heather M. McDiarmid Abstract Epithelial cells are the primary site of carcinogenesis in most tissues, including the mammary gland. As an alternative to the study of mutation induction in whole tissues in vivo, we have established Big BlueÔ transgenic rat cell lines from the mammary epithelium (BBR/ME) and the mammary stroma (BBR/MFib), to permit a comparison of their mutagenic responses to carcinogens. We previously demonstrated their responsiveness to the alkylating agent N -ethyl- N -nitrosourea (ENU) (McDiarmid H et al. [2001]: Mutat Res 497:39,47). Here, we examined the responses of cultured epithelial and stromal cells to the protein pyrolysis product and mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Rat hepatic S9 was used as a source of bioactivation enzymes. Mutant induction (cII locus) and clonogenic survival were measured as a function of PhIP concentration. PhIP mutagenicity was observed in the fibroblast cells, but the greater toxicity of PhIP to the epithelial cells prevented a definitive evaluation of mutagenicity. Since PhIP may be detoxified by conjugation with glutathione, we measured glutathione levels and glutathione- S -transferase expression and activities in both cell lines. The epithelial cells had higher glutathione- S -transferase enzyme activity and protein expression than did the fibroblast cell line. Because the epithelial cells were more sensitive to toxicity, glutathione conjugation evidently plays only a minor role in PhIP toxicity and mutagenicity in our cell lines. Environ. Mol. Mutagen. 39:245,253, 2002. © 2002 Wiley-Liss, Inc. [source] Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in miceENVIRONMENTAL TOXICOLOGY, Issue 5 2007R. Jayaraj Abstract Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem in several industrialized areas of the world. Microcystin-LR (MC-LR) is a cyanobacterial heptapeptide that represents acute and chronic hazards to animal and human health. Identification of suitable chemprotectants against microcystin is essential considering human health hazards. In the present study, we have evaluated the protective efficacy of three flavanoids namely quercetin (200 mg/kg), silybin (400 mg/kg), and morin (400 mg/kg)] pretreatment against microcystin toxicity (0.75 LD50, 57.5 ,g/kg) in mice. Various biochemical variables were measured to study the recovery profile of protected animals at 1- and 3-days post-toxin treatment. The serum alanine amino transferase (ALT) shows 17-fold increase in MC-LR treated animals compared with control group at 1 day. The silybin and quercetin group showed a decrease in level of ALT compared with MC-LR group but still higher than control group. No significant protection was observed with aspartate aminotransaminase (AST) and lactate dehydrogenase (LDH) levels in flavanoid-treated groups at 1-day post-treatment. But at 3 days, the serum levels of AST and ALT were normalized to control values, but the serum LDH levels were still significantly higher than the control group. No significant changes were observed in glutathione peroxidase and reduced glutathione levels at both 1- and 3-day postexposure. The catalase activity shows a significant decrease in quercetin-treated animals at 3-day postexposure. The protein phosphatase was significantly inhibited in MC-LR group compared to control. The silybin pretreated group showed recovery after 1 day. At 3 days, the PPAse activity was reversed to control values in all the flavanoid-treated groups. Immunoblotting analysis showed microcystin-PPAse adduct in liver tissues of toxin-treated as well as flavanoid-treated mice even after 3 days. The results of this study show that flavanoids, quercetin, silybin, and morin could reverse the hepatotoxic effects of MC-LR in vivo. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 472,479, 2007. [source] Pharmaceutical industry effluent diluted 1:500 affects global gene expression, cytochrome P450 1A activity, and plasma phosphate in fish,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2009Lina Gunnarsson Abstract Patancheru, near Hyderabad, India, is a major production site for the global bulk drug market. Approximately 90 manufacturers send their wastewater to a common treatment plant in Patancheru. Extraordinary high levels of a wide range of pharmaceuticals have recently been demonstrated in the treated effluent. As little as 0.2% of this effluent can strongly reduce the growth rate of tadpoles, but the underlying mechanisms of toxicity are not known. To begin addressing how the effluent affects aquatic vertebrates, rainbow trout (Oncorhynchus mykiss) were exposed to 0.2% effluent for 5 d. Several physiological endpoints, together with effects on global hepatic gene expression patterns, were analyzed. The exposed fish showed both an induction of hepatic cytochrome P450 1A (CYP1A) gene expression, as well as enzyme activity. Clinical blood chemistry analyses revealed an increase in plasma phosphate levels, which in humans indicates impaired kidney function. Several oxidative stress-related genes were induced in the livers; however, no significant changes in antioxidant enzyme activities or in the hepatic glutathione levels were found. Furthermore, estrogen-regulated genes were slightly up-regulated following exposure, and moderate levels of estriol were detected in the effluent. The present study identifies changes in gene expression triggered by exposure to a high dilution of the effluent, supporting the hypothesis that these fish are responding to chemical exposure. The pattern of regulated genes may contribute to the identification of mechanisms of sublethal toxicity, as well as illuminate possible causative agents. [source] Glutathione depletion and cardiomyocyte apoptosis in viral myocarditisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2004V. Kytö Abstract Background, The course of viral myocarditis is highly variable. Oxidative stress and Bcl-2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. Apoptosis is difficult to detect and quantify in vivo. Therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus B3 myocarditis. Methods, BALB/c mice were infected with the cardiotropic coxsackievirus B3 variant. Glutathione (HPLC), cardiomyocyte apoptosis (TUNEL and caspase-3 cleavage), Bax and Bcl-XL mRNA expression (real time RT-PCR), histopathology and viral replication (plaque assay and real time RT-PCR) were measured from day 3 to day 20 after infection. Results, Infection caused severe myocarditis and led to progressive decrease of plasma glutathione levels. Myocardial mRNA levels of pro-apoptotic Bax and antiapoptotic Bcl-XL were significantly increased from day 3 onwards. Bax mRNA and ratio of Bax to Bcl-XL correlated with cardiomyocyte apoptosis (r = 0·77, P = < 0·001 and r 0·51, P < 0·01, respectively). Cardiomyocyte apoptosis was highest on day 5, coinciding with a rapid decline in plasma glutathione (r = ,0·52, P = 0·003). Conclusions, Systemic oxidative stress as indicated by decreased plasma glutathione levels coincides with cardiomyocyte apoptosis in experimental coxsackievirus myocarditis. Decreased plasma glutathione levels and changes in cardiac Bax and Bcl-XL mRNA expression identify a phase of myocarditis in which the potentially preventable cardiomyocyte apoptosis is mostly observed. [source] N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen speciesEXPERIMENTAL DERMATOLOGY, Issue 8 2010Bour-Jr Wang Please cite this paper as: N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen species. Experimental Dermatology 2010; 19: e191,e200. Abstract Background:, Chromium hypersensitivity is an important issue in occupational skin disease. When hexavalent chromium enters the cell, it can be reduced to trivalent chromium, resulting in the formation of reactive oxygen species (ROS). ROS are considered to play an important role in the progression of allergic contact dermatitis. N -acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. Aims:, We attempted to demonstrate that NAC could inhibit chromium hypersensitivity in a coadjuvant chromium-sensitized albino guinea pig model by counteracting the formation of ROS. Methods:, We utilized a coadjuvant chromium-sensitized albino guinea pig model to evaluate both the severity of the skin reaction by intradermal and epicutaneous elicitation tests and the sensitization rate of chromium hypersensitivity in NAC-treated and NAC-untreated albino guinea pigs (GP). Furthermore, three ROS parameters, including H2O2, malondialdehyde (MDA) levels in the skin and the oxygen radical absorbance capacity (ORAC) in plasma, were analyzed in NAC-treated and NAC-untreated coadjuvant chromium-sensitized albino GP. Results:, The severity of the skin reaction in the intradermal and epicutaneous elicitation test significantly diminished when the albino GP were treated with a dose of 1200 mg/kg/day of NAC. This dose also significantly decreased the sensitization rate of chromium hypersensitivity. In addition, treatment with 1200 mg/kg/day of NAC significantly reduced the H2O2 and MDA levels in the skin and significantly increased the ORAC in the plasma of albino GP. Therefore, NAC could be a potential chemopreventative agent to prevent the progression of chromium hypersensitivity. [source] Cadmium blocks hypoxia-inducible factor (HIF)-1-mediated response to hypoxia by stimulating the proteasome-dependent degradation of HIF-1,FEBS JOURNAL, Issue 13 2000Yang-Sook Chun Cadmium is a substantial industrial and environmental pollutant which seriously impairs erythropoiesis. Cd has been demonstrated to aggravate anemia by suppressing erythropoietin gene expression in anemic patients. As hypoxic induction of erythropoietin mRNA depends on a transcription factor, hypoxia-inducible factor 1 (HIF-1), we hypothesized that Cd suppresses the hypoxic activation of HIF-1. In hypoxic Hep3B cells, all mRNAs of various genes, which are known to be upregulated by HIF-1 activation under hypoxia, were suppressed by Cd in a dose-dependent manner. Cd inhibited the hypoxia-induced activity of luciferase in 293 cells which was transfected with a reporter plasmid carrying a hypoxia response element. By electrophoretic mobility gel shift assay, Cd inhibited the DNA-binding activity of HIF-1 in hypoxic Hep3B cells. Cd reduced the amount of HIF-1, protein in hypoxia, whereas it didn't affect HIF-1 , mRNA levels. Moreover, Cd inhibited HIF-1, accumulation induced by cobalt and desferrioxamine. Antioxidants and a proteasome inhibitor prevented the HIF-1, degradation caused by Cd. The possibility that oxidative stress mediates this action of Cd was examined. Cd didn't affect protein oxidation and reduced glutathione levels in hypoxic cells. These results indicate that Cd triggers a redox/proteasome-dependent degradation of HIF-1, protein, reducing HIF-1 activity and in turn suppressing the hypoxic induction of hypoxia-inducible genes. [source] Combined therapy of silymarin and desferrioxamine in patients with ,-thalassemia major: a randomized double-blind clinical trialFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2009Marjan Gharagozloo Abstract Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3-month randomized, double-blind, clinical trial was conducted in 59 ,-thalassemia major patients in two well-matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin-treated ,-thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron-loaded patients. [source] The relationship between obesity and markers of oxidative stress in dogsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2009M. G. Cline Obesity, a serious epidemic affecting much of our pet population, increases the risk of developing numerous diseases. It has been demonstrated that obesity increases oxidative stress in obese children, cats and other species. Oxidative stress can result in DNA damage with subsequent alterations in gene expression, cell signaling, mutations, cell death or cell transformation. These effects of oxidative damage predispose animals and humans to numerous disease processes and cancer. The objective of the study was to demonstrate that obese dogs are under oxidative stress resulting in DNA damage and decreased endogenous antioxidant protection measured by serum glutathione levels and the ratio of reduced (GSH) to oxidized (GSSG) glutathione. In this case,control study, 10 obese dogs were compared with aged-matched healthy control dogs. Dogs with BCS of 7 or greater (9 pt scale) were considered obese. Dogs were evaluated by history, physical exam, body condition score, CBC, serum biochemical analysis and total T4, with both groups showing no significant differences in CBC, serum biochemical or T4 analysis. Single-cell gel electrophoresis (Comet assay) was used to measure DNA damage, and high performance liquid chromatography was used to measure serum glutathione. Reduced glutathione levels were significantly higher in the obese group (p = 0.012). The results of this pilot study suggest that obesity is associated with an increase in antioxidant potential, therefore justifying a larger study with antioxidant supplementation to determine how antioxidants in weight loss diets effects endogenous antioxidant capabilities. [source] A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitisJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2007L. Peran Abstract Aims:, The intestinal anti-inflammatory effects of three probiotics with immunomodulatory properties, Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium lactis, were evaluated and compared in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Methods and Results:, Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissolved in 0·25 ml of 50% ethanol. Each probiotic was administered orally (5 × 108 CFU suspended in 0·5 ml of skimmed milk) for 3 weeks, starting 2 weeks before the administration of TNBS. Colonic damage was evaluated histologically and biochemically 1 week after TNBS instillation. The results obtained revealed that all probiotics assayed showed intestinal anti-inflammatory effects, macroscopically evidenced by a significant reduction in the colonic weight/length ratio. Only B. lactis showed a lower incidence of diarrhoea in comparison with untreated rats. Biochemically, all probiotics restored colonic glutathione levels, depleted as a consequence of the oxidative stress of the inflammatory process. Bifidobacterium lactis treatment reduced colonic tumour necrosis factor (TNF)-, production, and inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression; L. acidophilus administration reduced colonic leukotriene B4 production and iNOS expression and L. casei intake was associated with a decrease in colonic COX-2 expression. Conclusion:, The three probiotics assayed have shown intestinal anti-inflammatory activity in the TNBS model of rat colitis, although each probiotic shows its own anti-inflammatory profile. Significance and Impact of the Study:, These probiotics could be considered as potential adjuvants in the treatment of inflammatory bowel disease, although more studies are required in order to demonstrate their efficacy in humans. [source] Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levelsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. M. ENGEL Background: Cardiac surgery with an extracorporeal circulation cardiopulmonary bypass (CPB) is characterized by an oxidative stress response. Glutathione (GSH) belongs to the major antioxidative defense. In metabolic stress, glutamine (GLN) may be the rate-limiting factor of GSH synthesis. Decreased GLN plasma levels were observed after various critical states. We evaluated, in patients undergoing open heart surgery with CPB, the effects of a peri-operative GLN supplementation on GSH in whole blood and assessed their influence on the Sequential Organ Failure Assessment score and the intensive care unit length of stay. Methods: In this prospective, randomized, double-blinded study, we included 60 patients (age older than 70 years, ejection fraction <40% or mitral valve replacement) undergoing an elective cardiac surgery with CPB. We randomly assigned each subject to receive an infusion with either GLN (0.5 g/kg/day, group 1) or an isonitrogeneous, isocaloric, isovolemic amino acids solution (group 2) or saline (group 3). Results: From the first post-operative day GLN plasma levels in group 1 were significantly increased compared with the other groups. With saline GSH the levels decreased significantly post-operatively compared with GLN. We observed a significant correlation between GLN delivery and GSH levels. Conclusions: A peri-operative high-dose GLN infusion increased plasma GLN concentrations and maintained the GSH levels after cardiac surgery with CPB. [source] Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercuryJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2010Rakhi Agarwal Abstract Curcumin, a safe nutritional component and a highly promising natural antioxidant with a wide spectrum of biological functions, has been examined in several metal toxicity studies, but its role in protection against mercury toxicity has not been investigated. Therefore, the detoxification and antioxidant effects of curcumin were examined to determine its prophylactic/therapeutic role in rats experimentally exposed to mercury (in the from of mercuric chloride-HgCl2, 12,µmol,kg,1 b.w. single intraperitoneal injection). Curcumin treatment (80,mg,kg,1 b.w. daily for 3 days, orally) was found to have a protective effect on mercury-induced oxidative stress parameters, namely, lipid peroxidation and glutathione levels and superoxide dismutase, glutathione peroxidase and catalase activities in the liver, kidney and brain. Curcumin treatment was also effective for reversing mercury-induced serum biochemical changes, which are the markers of liver and kidney injury. Mercury concentration in the tissues was also decreased by the pre/post-treatment with curcumin. However, histopathological alterations in the liver and kidney were not reversed by curcumin treatment. Mercury exposure resulted in the induction of metallothionein (MT) mRNA expressions in the liver and kidney. Metallothionein mRNA expression levels were found to decrease after the pre-treatment with curcumin, whereas post-treatment with curcumin further increased MT mRNA expression levels. Our findings suggest that curcumin pretreatment has a protective effect and that curcumin can be used as a therapeutic agent in mercury intoxication. The study indicates that curcumin, an effective antioxidant, may have a protective effect through its routine dietary intake against mercury exposure. [source] Diabetes, oxidative stress, and antioxidants: A reviewJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2003A. C. Maritim Abstract Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:24,38, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10058 [source] Glutamate is a determinant of cellular proliferation through modulation of nuclear factor E2 p45-related factor-2 expression in osteoblastic MC3T3-E1 cells,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007Kyosuke Uno Activation of particular glutamate (Glu) receptors is shown to promote cellular differentiation toward maturation during osteoblastogenesis. In the present study, we have evaluated the possible modulation by Glu of cellular proliferation in osteoblastic cells endowed to proliferate for self-renewal and to differentiate toward matured osteoblasts. Exposure to Glu significantly suppressed the proliferation activity at a concentration over 500 µM without inducing cell death in osteoblastic MC3T3-E1 cells before differentiation. The suppression by Glu occurred in a manner sensitive to the prevention by either cystine or reduced glutathione. Expression of mRNA was for the first time shown with the cystine/Glu antiporter composed of xCT and 4F2hc subunits in these undifferentiated osteoblastic cells. A significant decrease was seen in intracellular total glutathione levels in undifferentiated MC3T3-E1 cells cultured with Glu, indeed, whereas the cellular proliferation activity was drastically decreased by the addition of the glutathione depleter cyclohexene-1-one and the glutathione biosynthesis inhibitor L -buthionine-[S,R]-sulfoximine, respectively. Exposure to Glu led to a significant increase in mRNA expression of nuclear factor E2 p45-related factor 2 (Nrf2) together with the generation of reactive oxygen species, while a significant decrease was seen in the proliferation activity in MC3T3-E1 cells with stable overexpression of Nrf2. These results suggest that Glu could suppress the cellular proliferation toward self-renewal through a mechanism associated with the upregulation of Nrf2 expression in association with the depletion of intracellular glutathione after promoting the retrograde operation of the cystine/Glu antiporter in undifferentiated MC3T3-E1 cells. J. Cell. Physiol. 213: 105,114, 2007. © 2007 Wiley-Liss, Inc. [source] A novel approach to enhancing cellular glutathione levelsJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Pamela Maher Abstract GSH and GSH-associated metabolism provide the major line of defense for the protection of cells from oxidative and other forms of toxic stress. Of the three amino acids that comprise GSH, cysteine is limiting for GSH synthesis. As extracellularly cysteine is readily oxidized to form cystine, cystine transport mechanisms are essential to provide cells with cysteine. Cystine uptake is mediated by system xc,, a Na+ -independent cystine/glutamate antiporter. Inhibition of system xc, by millimolar concentrations of glutamate, a pathway termed oxidative glutamate toxicity, results in GSH depletion and nerve cell death. Recently, we described a series of compounds derived from the conjugation of epicatechin (EC) with cysteine and cysteine derivatives that protected nerve cells in culture from oxidative glutamate toxicity by maintaining GSH levels. In this study, we characterize an additional EC conjugate, cysteamine-EC, that is 5- to 10-fold more potent than the earlier conjugates. In addition, we show that these EC conjugates maintain GSH levels by enhancing the uptake of cystine into cells through induction of a disulfide exchange reaction, thereby uncoupling the uptake from system xc,. Thus, these novel EC conjugates have the potential to enhance GSH synthesis under a wide variety of forms of toxic stress. [source] Altered arachidonic acid biosynthesis and antioxidant protection mechanisms in Schwann cells grown in elevated glucoseJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Cristinel Mîinea Abstract In cultured Schwann cells, elevated glucose induces alterations in arachidonic acid metabolism that cause a decrease in the content of glycerophospholipid arachidonoyl-containing molecular species (ACMS). This could result from decreased de novo arachidonic acid biosynthesis, or increased arachidonic acid release from phospholipids. Incorporation of radioactive 8,11,14-eicosatrienoic acid into ACMS was lower for cells grown in 30 mm versus 5 mm glucose, consistent with a decrease in ,5 desaturase activity. However, neither basal arachidonic acid release from prelabeled cells nor stimulated generation of arachidonic acid in the presence of the reacylation inhibitor, thimerosal, the phosphotyrosine phosphatase inhibitor, bipyridyl peroxovanadium, or both together, were altered by varying the glucose concentrations, indicating that arachidonic acid turnover did not contribute to ACMS depletion. Free cytosolic NAD+/NADH decreased, whereas NADP+/NADPH remained unchanged for cells grown in elevated glucose, implying that decreased desaturase activity is a result of metabolic changes other than cofactor availability. Schwann cells in elevated glucose were susceptible to oxidative stress, as shown by increased malondialdehyde, depleted glutathione levels, and reduced cytosolic superoxide dismutase activity. Glutathione-altering compounds had no effect on ACMS levels, in contrast to N -acetylcysteine and ,-lipoic acid, which partly corrected ACMS depletion in phosphatidylcholine. These findings suggest that in the Schwann cell cultures, a high glucose level elicits oxidative stress and weakens antioxidant protection mechanisms which could decrease arachidonic acid biosynthesis and that this deficit can be partly corrected by treatment with exogenous antioxidants. [source] | ||||||||||||||||