Home About us Contact
|
Home About us Contact | ||
|
|
||
Glutathione Peroxidase Activity (glutathione + peroxidase_activity)
Selected AbstractsSynthesis of a New Seleninic Acid Anhydride and Mechanistic Studies into Its Glutathione Peroxidase ActivityCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2008Sun-Chol Yu Dr. Abstract Starting from low toxic salicyloylglycine, a new seleninic acid anhydride 7 that lacks Se,,,N or Se,,,O non-bonded interactions was synthesized. This compound exhibits a fourfold higher glutathione peroxidase-like (GPx-like) activity than ebselen and inhibits plant and mammalian 12/15-lipoxygenases at lower micromolar concentrations. Because of these pharmacological properties, 7 may constitute a new lead compound for the development of anti-inflammatory low-molecular-weight seleno-organic compounds. Analyzing the redox products of 7 with glutathione (GSH) and tBuOOH, we identified three potential catalytic cycles (A, B, C) of GPx-like activity that are interconnected by key metabolites. To study the relative contribution of these cycles to the catalytic activity, we prepared selected reaction intermediates and found that the activity of seleninic acid anhydride 7 and of the corresponding diselenide 11 and selenol 14 compounds were in the same range. In contrast, the GPx-like activity of monoselenide 9 was more than one order of magnitude lower. These data suggested that cycles A and B may constitute the major routes of GPx-like activity of 7, whereas cycle C may not significantly contribute to catalysis. [source] The lowering effect of high copper intake on selenium retention in weanling rats depends on the selenium concentration of the dietJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2001S. Yu The question addressed was whether the influence of dietary copper concentration on selenium metabolism depends on the amount of selenium in the diet. Weanling, male rats were fed purified diets containing either 1 (low), 4 (normal) or 42 (high) mg Cu/kg diet and either 0.03 (low), 0.05 (normal) or 1.0 (high) mg Se/kg diet in a 32 factorial design. Extra copper was added to the diets in the form of CuSO4,·,5H2O and selenium as Na2SeO3,·,5H2O. In rats fed either the low or normal amounts of selenium, higher intakes of copper decreased the apparent intestinal selenium absorption and increased urinary selenium excretion. The effects of copper on selenium absorption, excretion and retention were not seen in rats fed the high-selenium diets. An increase in dietary copper concentrations elevated selenium concentrations in the liver and kidneys, but slightly lowered those in the spleen of rats that were fed the diets with the normal level of selenium. In rats that were fed the diets with either low or high selenium concentration, copper intake had no effect on organ selenium concentrations. Glutathione peroxidase activity in erythrocytes was raised by feeding the diets which contained either normal or high copper content instead of those that were low in copper. It is concluded that the amount of selenium in the diet determines whether or not an increase in dietary copper concentration affects selenium metabolism. [source] Protective effects of quercetin on ultraviolet A light-induced oxidative stress in the blood of ratJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2002Ahmet Kahraman Abstract The oxidative effects of ultraviolet A (UVA) light (320,400 nm) and the antioxidant effects of quercetin were examined in rat blood. For this purpose, rats were divided into three groups: control, ultraviolet (UV) and ultraviolet + quercetin (UV + Q). The UV and UV + Q groups were irradiated for 4 h a day with UVA light (1.25 mW cm2) during periods of 3, 6 and 9 days. Quercetin (50 mg kg,1 body wt.) was administered intraperitoneally in the UV + Q group rats before irradiation periods. Blood was taken 3, 6 and 9 days post-treatment. Plasma malondialdehyde (MDA) levels significantly increased after 9 days of daily exposure to UVA. Whole blood glutathione (GSH) levels significantly declined after 3,9 days of irradiation. Glutathione peroxidase activity on days 6 and 9 and glutathione reductase activities on days 3, 6 and 9 post-irradiation were diminished significantly. Superoxide dismutase and catalase activities decreased significantly 3,9 days post-irradiation. The administration of quercetin before the 9-day period of irradiation significantly reduced the increase in plasma MDA value. Whole blood GSH levels significantly decreased with the administration of quercetin on all days. Quercetin significantly increased antioxidant enzymes diminished by UVA irradiation. Exposure of rats to UVA light leads to oxidative stress, reflected by increased MDA and reduced antioxidant enzyme levels. The administration of quercetin appears to be a useful approach to reduce the damage produced by UVA radiation. Copyright © 2002 John Wiley & Sons, Ltd. [source] Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelinANDROLOGIA, Issue 6 2009A. Kheradmand Summary Ghrelin has recently been reported to exert beneficial effects on various oxidative stresses as a result of its antioxidant properties. Therefore, we designed this study to explore the probable antioxidative effects of this peptide in the testis. Twenty-eight male adult Wistar rats were divided into equal control and treatment groups. In the treatment group, 1 nmol of ghrelin was administered as subcutaneous injection for 10 consecutive days or vehicle (physiological saline) to the control rats. The control and treated rats were killed on days 6 and 10 after beginning of ghrelin injection (n = 7 from each group on each day). The testes were taken and measured for antioxidant enzyme activity and malondialdehyde (MDA) content. Glutathione peroxidase activity significantly increased on day 10 in the treated animals compared with the control group (P < 0.05). Although the mean activity of glutathione peroxidase was greater on day 6 in the ghrelin-treated group than in the control animals, it was not statistically significant. There were no significant differences in superoxide dismutase and catalase activities between the groups. However, MDA level decreased by ghrelin treatment on day 10 compared with the control rats (P < 0.05). The results of this study indicate for the first time novel evidences for antioxidant properties of ghrelin in the rat testis. [source] Glutathione peroxidase activity modulates recovery in the injured immature brain,ANNALS OF NEUROLOGY, Issue 5 2009Kyoko Tsuru-Aoyagi MD Objective Mice subjected to traumatic brain injury at postnatal day 21 show emerging cognitive deficits that coincide with hippocampal neuronal loss. Here we consider glutathione peroxidase (GPx) activity as a determinant of recovery in the injured immature brain. Methods Wild-type and transgenic (GPxTg) mice overexpressing GPx were subjected to traumatic brain injury or sham surgery at postnatal day 21. Animals were killed acutely (3 or 24 hours after injury) to assess oxidative stress and cell injury in the hippocampus or 4 months after injury after behavioral assessments. Results In the acutely injured brains, a reduction in oxidative stress markers including nitrotyrosine was seen in the injured GPxTg group relative to wild-type control mice. In contrast, cell injury, with marked vulnerability in the dentate gyrus, was apparent despite no differences between genotypes. Magnetic resonance imaging demonstrated an emerging cortical lesion during brain maturation that was also indistinguishable between injured genotypes. Stereological analyses of cortical volumes likewise confirmed no genotypic differences between injured groups. However, behavioral tests beginning 3 months after injury demonstrated improved spatial memory learning in the GPxTg group. Moreover, stereological analysis within hippocampal subregions demonstrated a significantly greater number of neurons within the dentate of the GPx group. Interpretation Our results implicate GPx in recovery of spatial memory after traumatic brain injury. This recovery may be attributed, in part, to a reduction in early oxidative stress and selective, long-term sparing of neurons in the dentate. Ann Neurol 2009;65:540,549 [source] Effect of di(n -butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid ratsENVIRONMENTAL TOXICOLOGY, Issue 3 2007Ena Lee Abstract This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 ,g/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor ,-1 (TR,-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 245,255, 2007. [source] E6* oncoprotein expression of human papillomavirus type-16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defenceEXPERIMENTAL DERMATOLOGY, Issue 6 2005Stéphane Mouret Abstract:, Clinical observations of non-melanoma skin cancer in immunocompromised patients, such as organ transplant recipients, suggest co-operative effects of human papillomavirus (HPV) and ultraviolet (UV) radiation. The aim of the present study is to evaluate UV sensitivity and DNA damage formation according to antioxidant status in HPV16-infected keratinocytes. We used SKv cell lines, infected with HPV16 and well characterized for their proliferative and tumorigenic capacities. We showed that SKv cell lines presented various E6* (a truncated form of E6) RNA levels. We demonstrated that the higher oncoprotein RNA expression level was associated with a higher resistance to solar-simulated radiation, more specifically to UVB radiation and to hydrogen peroxide. Moreover, this high resistance was associated with a low oxidative DNA damage formation after UV radiation and was related to high glutathione content and glutathione peroxidase activities. Therefore, the results of our study suggest that E6* levels could modulate the glutathione/glutathione peroxidase pathway providing a mechanism to protect HPV-infected keratinocytes against an environmental oxidative stress, such as UV radiation. [source] Determination of the selenium requirement in kittens,JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 9-10 2003K. J. Wedekind Summary The purpose of this study was to determine the selenium (Se) requirement in kittens. Thirty-six specific-pathogen-free kittens (9.8 weeks old) were utilized in a randomized complete block design to determine the Se requirement in cats with gender and weight used as blocking criteria. Kittens were fed a low Se (0.02 mg/kg Se) torula yeast-based diet for 5 weeks (pre-test) after which an amino acid-based diet (0.027 mg Se/kg diet) was fed for 8 weeks (experimental period). Six levels of Se (0, 0.05, 0.075, 0.10, 0.20 and 0.30 mg Se/kg diet) as Na2SeO3 were added to the diet and were used to construct a response curve. Response variables included Se concentrations and Se-dependent glutathione peroxidase activities (GSHpx) in plasma and red blood cells (RBC) as well as plasma total T3 (TT3) and total T4 (TT4). No significant changes in food intake, weight gain or clinical signs of Se deficiency were noted. Estimates of the kitten's Se requirement (i.e. breakpoints) were determined for RBC and plasma GSHpx (0.12 and 0.15 mg Se/kg diet, respectively), but no definitive breakpoint was determined for plasma Se. Plasma TT3 increased linearly, whereas plasma TT4 and the ratio of TT4 : TT3 decreased in a quadratic fashion to dietary Se concentration. The requirement estimate determined in this study (0.15 mg Se/kg) for kittens is in close agreement with other species. As pet foods for cats contain a high proportion of animal protein with a Se bioavailability of 30%, it is recommended that commercial diets for cats contain 0.5 mg Se/kg DM. [source] Ethanol-induced alterations of the antioxidant defense system in rat kidneyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2006Diana Dinu Abstract We report here the effects of chronic ethanol consumption on the antioxidant defense system in rat kidney. Thirty-two male Wistar rats were randomly divided in two identical groups and were treated as follows: control group (water for fluid) and the ethanol-fed group (2 g/kg body weight/24 h). The animals were sacrificed after 10 weeks, and respectively 30 weeks of ethanol consumption, and the renal tissue was isolated and analyzed. Results revealed that kidney alcohol dehydrogenase activities increased significantly after ethanol administration, but the electrophoretic pattern of alcohol dehydrogenase isoforms was unmodified. The SDS polyacrylamidegel electrophoretic study of kidney proteins has revealed the appearance of two new protein bands after long-term ethanol consumption. The kidney reduced glutathione/oxidized glutathione ratio decreased, indicating an oxidative stress response due to ethanol ingestion. The malondialdehyde contents and xanthine oxidase activities were unchanged. The antioxidant enzymatic defense system showed a different response during the two periods of ethanol administration. After 10 weeks, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were activated, while superoxide dismutase, glutathione transferase, and ,-glutamyltranspeptidase levels were stationary. After 30 weeks, superoxide dismutase and glutathione peroxidase activities were unmodified, but catalase, glutathione transferase, ,-glutamyltranspeptidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities were significantly increased. Remarkable changes have been registered after 30 weeks of ethanol administration for glutathione reductase and glucose-6-phosphate dehydrogenase activities, including an increase by 106 and 216' of control values, respectively. These results showed specific changes in rat kidney antioxidant system and glutathione status as a consequence of long-term ethanol administration. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:386-395, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20101 [source] Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2001Ruth A. Sanders Abstract In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:143,149, 2001 [source] Mutagenic Safety and Fatty Liver Improvement of Nanonized Black Soybeans in Senescence-Accelerated Prone-8 MiceJOURNAL OF FOOD SCIENCE, Issue 5 2010J.-W. Liao Abstract:, Nanotechnology, as a new enabling technology, has the potential to revolutionize food systems. However, much attention has been focused on nanoparticle foods due to their potential physiological properties. This study was aimed to evaluate the mutagenic safety and fatty liver improvement of black soybean in senescence-accelerated mice (SAMP8). The mutagenic activity of black soybeans was investigated using the Ames test (Salmonella Typhimurium,TA98, 100, 102, and 1535). Furthermore, senescence-accelerated prone-8 mice (SAMP8) have been reported to display spontaneous fatty liver. Male SAMP8 mice were divided into control and supplemented with 10% micronized or nanonized black soybeans diet and fed for 12 wk. The results revealed that the Ames test of micronized and nanonized black soybeans exhibited no mutagenicity. Administration of black soybeans to mice showed no effects on food intake and body and organ weights. The nanonized black soybean group had a lower degree of spontaneous fatty liver, alanine aminotransferase, and thiobarbituric acid-reactive substance concentrations, and had enhanced superoxide dismutase, catalase, and glutathione peroxidase activities of livers when compared with the SAMP8 control and micronized black soybean groups. The mice fed with black soybeans had significantly lower triglyceride concentrations than the SAMP8 control group. The results of this study suggest that nanonized black soybeans have no side effects and, moreover, may minimize liver lesions in SAMP8 mice. [source] Altered anti-oxidant status and increased lipid peroxidation in marasmic childrenPEDIATRICS INTERNATIONAL, Issue 3 2000M Mansur Tatli Abstract Background: Protein energy malnutrition (PEM) is a common pediatric health problem in developing countries. Although the clinical features of PEM are well known, its pathophysiology is still unclear. Free radicals have been implicated in pathogenesis of PEM. In the present study, oxidant/anti-oxidant status in marasmus was investigated. Methods: Red cell glutathione, glutathione peroxidase and superoxide dismutase and their related cofactors, serum selenium and copper, were studied in marasmic and control children. Serum lipid peroxidation was also evaluated to assess oxidative stress. Results: The red cell glutathione levels and glutathione peroxidase activities were found to be significantly lower in the marasmic children than in the controls. Red cell superoxide dismutase (SOD) activity was not different between two groups. Serum selenium and copper concentrations were significantly lower in the marasmic children than in the control subjects. The malondialdehyde concentration, which is an index of lipid peroxidation, was significantly higher in the marasmic group compared with the controls. Conclusion: The anti-oxidant defense system was affected in marasmic children. Reduced anti-oxidant status and increased oxidative stress occurs in marasmic children. [source] Synthesis of New Quinoline Derivatives as Inhibitors of Human Tumor Cells GrowthARCHIV DER PHARMAZIE, Issue 8 2010Aymn E. Rashad Abstract A series of new 8-[(2H -tetrazol-5-yl)methoxy]quinoline derivatives, their sugar hydrazones, and their N -glycoside derivatives were synthesized. Furthermore, the 1,2,4-triazole-3-one derivatives 3 and 4 were synthesized from the amidrazone derivative 2. Some of the newly prepared compounds demonstrated inhibitory effects on the growth of MCF-7 human breast cancer cells as compared with the activity of the commonly used anticancer drug, cisplatin. The results of antitumor evaluation revealed that compounds 2,5, 8b, and 12 inhibited the growth of cancer cells through their effect as free-radical regulators by increasing the activity of superoxide dismutase and depletion of intracellular levels of reduced glutathione, catalase and glutathione peroxidase activities, accompanied with a high production of hydrogen peroxide, nitric oxide, and other free radicals causing the killing of tumor cells. The results suggested that the prepared compounds possess significant anticancer activity comparable to cisplatin and the antitumor activity of these prepared compounds was accompanied with a reduction in the levels of protein and nucleic acids. [source] Plasma xanthine oxidase, superoxide dismutase and glutathione peroxidase activities and uric acid levels in severe and mild pre-eclampsiaCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2004Abdulkadir Yildirim Abstract The aim of the present study was to measure plasma uric acid (UA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) activities and to evaluate the relationship between these parameters and the severity of pre-eclampsia. Twenty-five pre-eclamptic, 15 healthy pregnant and 15 non-pregnant women were enrolled in this study. Increased mean plasma XO activity was found to be higher in both pre-eclampsia groups than in the healthy pregnant group. Plasma UA levels were the highest in the severe pre-eclampsia group among the study groups. SOD and GSH-Px activities were significantly lower in both pre-eclampsia groups than in the healthy pregnant group (p,<,0.005 and p,<,0.001, respectively). Increased XO and decreased SOD and GSH-Px activities may contribute to the pathophysiological mechanisms of pre-eclampsia and increased UA may serve a protective role responding to superoxide radicals arising from increased XO activity or other sources in pre-eclampsia. Copyright © 2004 John Wiley & Sons, Ltd. [source] Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbitsCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2002M. Kemal Irmak Abstract The number of reports on the effects induced by electromagnetic radiation (EMR) in various cellular systems is still increasing. Until now no satisfactory mechanism has been proposed to explain the biological effects of this radiation. Oxygen free radicals may play a role in mechanisms of adverse effects of EMR. This study was undertaken to investigate the influence of electromagnetic radiation of a digital GSM mobile telephone (900,MHz) on oxidant and antioxidant levels in rabbits. Adenosine deaminase, xanthine oxidase, catalase, myeloperoxidase, superoxide dismutase (SOD) and glutathione peroxidase activities as well as nitric oxide (NO) and malondialdehyde levels were measured in sera and brains of EMR-exposed and sham-exposed rabbits. Serum SOD activity increased, and serum NO levels decreased in EMR-exposed animals compared to the sham group. Other parameters were not changed in either group. This finding may indicate the possible role of increased oxidative stress in the pathophysiology of adverse effect of EMR. Decreased NO levels may also suggest a probable role of NO in the adverse effect. Copyright © 2002 John Wiley & Sons, Ltd. [source] EPIGALLOCATECHIN-3-GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN-ACTIVATED PROTEIN KINASE SIGNALSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2009Dan-Dan Chen SUMMARY 1It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and ,-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52%vs TAC, respectively), accompanied by significant inhibition of nuclear factor-,B and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats. 4In conclusion, EGCG attenuates TAC-induced ventricular hypertrophy in hypertensive rats in part by suppression of anti-oxidant enzymes and regulation of MAPK signals. [source] Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2008T. Kaur SUMMARY., The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course. [source] Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinomaHEPATOLOGY, Issue 6 2004Christoph Jüngst Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2,-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C , T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH). The aim of this study was to evaluate the extent of oxidative damage and its dependence on the cellular antioxidative capacity and the expression of specific DNA repair enzymes in tumor (tu) and corresponding adjacent nontumor (ntu) liver tissue of 23 patients with histologically confirmed hepatocellular carcinoma. 8-oxo-dG levels, as detected by high-pressure liquid chromatography with electrochemical detection, were significantly (P = .003) elevated in ntu tissue (median, 129 fmol/,g DNA) as compared to tu tissue (median, 52 fmol/,g DNA), and were closely associated with inflammatory infiltration. In ntu tissue, the hepatic iron concentration and malondialdehyde levels were significantly (P = .001) higher as compared to tu tissue. Glutathione content, glutathione peroxidase activity and manganese superoxide dismutase messenger RNA (mRNA) expression did not show statistical differences between ntu and tu tissue. Real-time reverse transcription polymerase chain reaction revealed in tu tissue significantly (P = .014) higher hMTH1 mRNA expression compared to ntu tissue. In contrast, hMYH mRNA expression was significantly (P < .05) higher in ntu tissue. No difference in hOGG1 mRNA expression was seen between tu and ntu. In conclusion, these data suggest that ROS generated by chronic inflammation contribute to human hepatocarcinogenesis. The role of DNA repair enzymes appears to be of reactive rather than causative manner. (HEPATOLOGY 2004;39:1663,1672.) [source] Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2001Ruth A. Sanders Abstract In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:143,149, 2001 [source] Selenium Deficiency-Induced Growth Retardation Is Associated with an Impaired Bone Metabolism and OsteopeniaJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2001Rodrigo Moreno-Reyes Abstract Although the importance of selenium for bone metabolism is unknown, some clinical conditions such as Kashin-Beck osteoarthropathy have been associated with selenium deficiency. Although selenium deficiency induces growth retardation in rats, it has not been established whether this growth inhibition is associated with changes in bone metabolism. We investigated the effect of selenium deficiency on bone metabolism in growing male rats fed a selenium-deficient diet for two generations (Se,). In Se, rats, erythrocyte glutathione peroxidase activity and plasma selenium concentration were strongly reduced compared with pair-fed selenium-adequate rats (Se+). Weight and tail length were reduced by 31% and 13% in the Se, rats, respectively (p < 0.001). The Se, diet was associated with a 68% reduction of pituitary growth hormone (GH; p = 0.01) and a 50% reduction of plasma insulin-like growth factor I (IGF-I; p < 0.001). Plasma calcium was lower and urinary calcium concentration was greater in Se, rats. This group had a 2-fold increase in parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in plasma. Plasma osteocalcin and urinary deoxypyridoline were reduced by 25% and 57% in the Se, rats (p < 0.001). Selenium deficiency resulted in a 23% and 21% reduction in bone mineral density (BMD) of the femur and tibia (p < 0.001) and this effect persisted after adjustment for weight in a linear regression model. A 43% reduction in trabecular bone volume of the femoral metaphysis (p < 0.001) was found in Se, rats. This experimental study shows that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and osteopenia in second-generation selenium-deficient rats. [source] Human catalytic antibody Se-scFv-B3 with high glutathione peroxidase activityJOURNAL OF MOLECULAR RECOGNITION, Issue 5 2008Rui Huo Abstract In order to generate catalytic antibodies with glutathione peroxidase (GPX) activity, we prepared GSH-S-2,4-dinitrophenyl t -butyl ester (GSH-S-DNPBu) as target antigen. Three clones (A11, B3, and D5) that bound specifically to the antigen were selected from the phage display antibody library (human synthetic VH,+,VL single-chain Fv fragment (scFv) library). Analysis of PCR products using gel electrophoresis and sequencing showed that only clone B3 beared intact scFv-encoding gene, which was cloned into the expression vector pPELB and expressed as soluble form (scFv-B3) in Escherichia coli Rosetta. The scFv-B3 was purified by Ni2+ -immobilized metal affinity chromatography (IMAC). The yield of purified proteins was about 2.0,3.0,mg of proteins from 1,L culture. After the active site serines of scFv-B3 were converted into selenocysteines (Secs) with the chemical modification method, we obtained the human catalytic antibody (Se-scFv-B3) with GPX activity of 1288,U/µmol. Copyright © 2008 John Wiley & Sons, Ltd. [source] Protective effect of Hachimi-jio-gan against renal failure in a subtotal nephrectomy rat modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2005Noriko Yamabe The protective effect of Hachimi-jio-gan extract against chronic renal failure in a subtotal nephrectomy rat model was investigated. The level of serum urea nitrogen by nephrectomy was increased over 15 weeks, but the administration of Hachimi-jio-gan at 50 and 200 mg led to the decrease. In addition, the levels of creatinine (Cr), urinary methylguanidine (MG) and MG/Cr were increased, whereas Cr clearance dramatically decreased in nephrectomized rats. However, oral administration of Hachimi-jio-gan extract prevented the elevation of these uremic toxins in serum and urine, and the production of hydroxyl radical. Moreover, nephrectomy led to a significant decline in superoxide dismutase (SOD) and catalase activities, but increased glutathione peroxidase activity compared with normal levels, indicating an abnormal antioxidative system. The increased activity of both SOD and catalase by the oral administration of Hachimi-jio-gan suggested that these enzymes are associated with the protective role of Hachimi-jio-gan extract against oxidative stress by nephrectomy. Moreover, the decrease in serum albumin in nephrectomized control rats was increased and proteinuria was ameliorated by the administration of Hachimi-jio-gan with improved glomerular hyalinosis, interstitial fibrosis and inflammation, suggesting the beneficial effect of Hachimi-jio-gan to prevent glomerular sclerosis and progressive renal fibrosis. This study suggests that Hachimi-jio-gan plays a protective role in the progression of chronic renal failure through the decline in uremic toxins, elevation of antioxidative enzyme activity such as SOD and catalase, and amelioration of histopathological lesions in the kidney. [source] Amelioration of doxorubicin-induced myocardial oxidative stress and immunosuppression by grape seed proanthocyanidins in tumour-bearing miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2005Xiao-Yu Zhang We have investigated the protective effects of grape seed proanthocyanidins on doxorubicin-induced toxicity in tumour-bearing mice. The intraperitoneal administration of doxorubicin (2 mg kg,1 every other day, cumulative dosage for 18 mg kg,1) significantly inhibited the growth of sarcoma 180, and induced myocardial oxidative stress with decreased superoxide dismutase and glutathione peroxidase activity while increasing malondialdehyde formation in the heart or serum. Doxorubicin-induced myocardial oxidative stress also reduced lactate dehydrogenase and creatine kinase activity in the heart and elevated their levels in the serum. Doxorubicin also affected immune functions of tumour-bearing mice with significantly decreased interleukin-2 (IL-2) and interferon-, (INF-,) production, and slightly decreased natural killer (NK) cell cytotoxicity, lymphocyte proliferation and CD4+/CD8+ ratio. It markedly increased the percentages of cytotoxic T cells (CD3+CD8+), helper T cells (CD3+CD4+), IL-2R+CD4+, and IL-2R+ cells as compared with untreated tumour-bearing mice. The intragastric administration of proanthocyanidin (200 mg kg,1 daily) significantly inhibited tumour growth, and increased NK cell cytotoxicity, lymphocyte proliferation, CD4+/CD8+ ratio, IL-2 and INF-, production. Moreover, proanthocyanidin strongly enhanced the anti-tumour effect of doxorubicin and the above immune responses, and completely eliminated myocardial oxidative stress induced by doxorubicin. In conclusion, intragastric administration of proanthocyanidin could enhance the anti-tumour activity of doxorubicin and ameliorate doxorubicin-induced myocardial oxidative stress and immunosuppression in tumour-bearing mice. [source] Melatonin increases glutathione peroxidase activity and deformability of erythrocytes in septic ratsJOURNAL OF PINEAL RESEARCH, Issue 2 2003M.B. Yerer No abstract is available for this article. [source] Melatonin stimulates glutathione peroxidase activity in human chorionJOURNAL OF PINEAL RESEARCH, Issue 4 2001Yuji Okatani In preeclampsia, placental production of lipid peroxides is abnormally increased, while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are decreased. Administration of melatonin, a powerful scavenger of oxygen free radicals, also may protect the placenta from free radical-induced damage by increasing the activity of antioxidant enzymes. To test this hypothesis we administered melatonin to pregnant women before they underwent voluntary interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was administered orally at 12:00 hr, and samples of chorion and maternal blood were obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the melatonin concentration in maternal serum and activities of GSH-Px and SOD and levels of melatonin in chorionic homogenates. Melatonin administration was reflected by markedly increased melatonin concentrations in maternal serum and in chorion, with peak levels achieved 1 hr after melatonin administration (serum, 46.87±10.87 nM/L; chorionic homogenate, 4.36±1.56 pmol/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic homogenates increased significantly (P<0.001), with peak levels occurring at 3 hr (51.68±3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated control subjects). No significant changes in chorionic SOD activity occurred during the 3-hr post-administration period. These results indicate that exogenous melatonin increases GSH-Px activity in the chorion and thereby may protect indirectly against free radical injury. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excessive free radical production, such as intrauterine fetal growth retardation and fetal hypoxia. [source] Panax ginseng reduces adriamycin-induced heart failure in ratsPHYTOTHERAPY RESEARCH, Issue 12 2005Jyh-Sheng You Abstract The purpose of this study was to investigate the protective effects of Panax ginseng on adriamycin-induced heart failure. Wistar rats were divided into four groups: control, adriamycin, ginseng and adriamycin with ginseng. Adriamycin (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks. Ginseng was administered via an oral feeding tube once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5 week post-treatment period, the hearts of the rats were used to study the synthesis rates of DNA, RNA and protein, myocardial antioxidants and lipid peroxidation. At the end of 3 weeks treatment, heart failure was characterized by ascites, congested liver and depressed cardiac function. Nucleic acid as well as protein synthesis was inhibited, lipid peroxidation was increased and myocardial glutathione peroxidase activity was decreased indicating adriamycin-induced heart failure. In contrast, the administration of ginseng, before and concurrent with adriamycin, significantly attenuated the myocardial effects, lowered the mortality as well as the amount of ascites, increased in myocardial glutathione peroxidase, macromolecular biosynthesis and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. These findings indicated that ginseng may be partially protective against adriamycin-induced heart failure. Copyright © 2005 John Wiley & Sons, Ltd. [source] Delayed Protection of Tetramethylpyrazine on Neonatal Rat Cardiomyocytes Subjected to Anoxia-Reoxygenation InjuryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2007He-Ping Chen Cultured neonatal rat cardiomyocytes were preconditioned using TMP at different concentrations (100, 200 and 500 µM). Cell viability, lactate dehydrogenase release, malondialdehyde formation, superoxide dismutase activity and glutathione peroxidase activity were measured to determine the protective effects against anoxia-reoxygenation injury. The expression of heat shock protein 70 (Hsp70) was measured 24 hr after TMP preconditioning by Western blot analysis. The results showed that TMP decreased lactate dehydrogenase release, increased cell viability, suppressed malondialdehyde formation and augmented activities of superoxide dismutase and glutathione peroxidase in a concentration-dependent manner. Moreover, the delayed protection was abolished by pre-treating with either protein kinase C inhibitor chelerythrine chloride or PD98059, a selective inhibitor of extracellular signal-regulated protein kinase 1/2, respectively, and the expression of Hsp70 was significantly increased in 24 hr after TMP preconditioning that was also suppressed by chelerythrine chloride or PD98059. These results suggest that TMP can induce delayed cardioprotective effects by activation of protein kinase C and extracellular signal-regulated protein kinase 1/2 signalling pathways and subsequent increased expression of Hsp70 in rat neonatal cardiomyocytes. [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] The effect of desferrioxamine on peroxynitrite-induced oxidative damage in erythrocytesCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2004Aytu Ertabak Abstract The aim of this study was to investigate the effect of desferrioxamine on peroxynitrite-mediated damage in erythrocytes by measuring the 3-nitrotyrosine level and glutathione peroxidase and Na+ -K+ ATPase activities in vitro. 3-Nitrotyrosine levels were determined by HPLC; glutathione peroxidase and Na+ -K+ ATPase activities were measured by spectrophotometry. Peroxynitrite increased the 3-nitrotyrosine level but decreased both enzyme activities. In the presence of desferrioxamine, glutathione peroxidase activity was increased with a decrease in the 3-nitrotyrosine level. Desferrioxamine was found to possess an important antioxidant activity as assessed in an in vitro system, reducing protein nitration, restorating enzyme activities and maintaining erythrocyte membrane integrity. Copyright © 2004 John Wiley & Sons, Ltd. [source] Antioxidant capacity of human milk: effect of thermal conditions for the pasteurizationACTA PAEDIATRICA, Issue 8 2008Dolores Silvestre Abstract Aim: Pasteurization is the thermal treatment usually applied in milk banks to eliminate the risk of transmission of infectious agents. The aim of this study was to investigate the effect of heat processing upon the antioxidant properties of human milk. Methods: Milk samples collected from 31 healthy women were subjected to two different pasteurization techniques: Holder pasteurization (63°C for 30 min) and high pasteurization (75°C for 15 sec) and oxidative stress markers (glutathione, glutathione peroxidase activity, malondialdehyde and total antioxidant capacity) were determined in comparison to fresh milk. Results: Malondialdehyde concentration was the same in all samples, while there was a decrease in glutathione concentration and total antioxidant capacity in milk samples subjected to thermal processing versus fresh milk samples. However, the drop in these parameters was seen to be significantly greater when applying Holder pasteurization. Both thermal treatments induced considerable and similar loss of glutathione peroxidase activity. Conclusion: Thermal processing of human milk implies a decrease in its antioxidant properties but, when necessary, high pasteurization should be the election method in terms of milk oxidative status. [source] | ||||||||||||||||||||||||||||