Home About us Contact
|
Home About us Contact | ||
|
|
||
GSH Content (gsh + content)
Selected AbstractsGlutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stressACTA PHYSIOLOGICA, Issue 1 2001S. Leichtweis The efficacy of glutathione (GSH) in protecting ischaemia-reperfusion (I-R) induced cardiac dysfunction and myocardial oxidative stress was studied in open-chest, stunned rat heart model. Female Sprague,Dawley rats were randomly divided into three experimental groups: (1) GSH-depletion, by injection of buthionine sulphoxamine (BSO, 4 mmol kg,1, i.p.) 24 h prior to I-R, (2) BSO injection (4 mmol kg,1, i.p.) in conjunction with acivicin (AT125, 0.05 mmol kg,1, i.v.) infusion 1 h prior to I-R, and (3) control (C), receiving saline treatment. Each group was further divided into I-R, with surgical occlusion of the main left coronary artery (LCA) for 30 min followed by 20 min reperfusion, and sham. Myocardial GSH content and GSH : glutathione disulphide (GSSG) ratio were decreased by ,50% (P < 0.01) in both BSO and BSO + AT125 vs. C. Ischaemia-reperfusion suppressed GSH in both left and right ventricles of C (P < 0.01) and left ventricles of BSO and BSO + AT125 (P < 0.05). Contractility (+dP/dt and ,dP/dt) in C heart decreased 55% (P < 0.01) after I and recovered 90% after I-R, whereas ±dP/dt in BSO decreased 57% (P < 0.01) with ischaemia and recovered 76 and 84% (P < 0.05), respectively, after I-R. For BSO + AT125, ±dP/dt were 64 and 76% (P < 0.01) lower after ischaemia, and recovered only 67 and 61% (P < 0.01) after I-R. Left ventricular systolic pressure in C, BSO and BSO + AT125 reached 95 (P > 0.05) 87 and 82% (P < 0.05) of their respective sham values after I-R. Rate-pressure double product was 11% (P > 0.05) and 25% (P < 0.05) lower in BSO and BSO + AT125, compared with Saline, respectively. BSO and BSO + AT125 rats demonstrated significantly lower liver GSH and heart Mn superoxide dismutase activity than C rats after I-R. These data indicate that GSH depletion by inhibition of its synthesis and transport can exacerbate cardiac dysfunction inflicted by in vivo I-R. Part of the aetiology may involve impaired myocardial antioxidant defenses and whole-body GSH homeostasis. [source] ,-Glutamyltranspeptidase,deficient knockout mice as a model to study the relationship between glutathione status, mitochondrial function, and cellular functionHEPATOLOGY, Issue 4 2000Yvonne Will ,-Glutamyltranspeptidase (GGT)-deficient mice (GGT,/,) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (<20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by ,50% in GGT,/, mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT,/, mice liver mitochondria were ,60% those of wild-type mice primarily as a result of impaired state 3 respiration. Mitochondrial adenine nucleotide content was decreased by ,40% in mitochondria obtained from GGT,/, mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (<50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT,/, knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT,/, mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT,/, mice with N -acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT,/, mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice. [source] Genistein selectively potentiates arsenic trioxide-induced apoptosis in human leukemia cells via reactive oxygen species generation and activation of reactive oxygen species-inducible protein kinases (p38-MAPK, AMPK)INTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Yolanda Sánchez Abstract The observation that genistein may behave as a pro-oxidant agent lead us to examine the capacity of this isoflavone to modulate the toxicity of the oxidation-sensitive anti-leukemic agent arsenic trioxide (ATO), and for comparison other anti-tumor drugs. Co-treatment with genistein increased ATO-provoked apoptosis and activated apoptosis regulatory events (Bcl-XL down-regulation, cytochrome c and Omi/HtrA2 release from mitochondria, XIAP decrease and caspase-8/Bid and caspase-3 activation) in U937 promonocytes and other human leukemia cell lines (HL60, THP-1, Jurkat, RPMI-8866), but not in phytohemagglutinin-stimulated non-tumor peripheral blood lymphocytes (PBLs). Genistein, alone and with ATO, stimulated reactive oxygen species generation, and apoptosis was attenuated by N -acetyl- L -cysteine and butylated hydroxyanisole. Addition of low H2O2 concentrations mimicked the capacity of genistein to increase ATO-provoked apoptosis in leukemia cells, but not in PBLs. By contrast, co-treatment with genistein or H2O2 failed to potentiate the toxicity of DNA-targeting agent cisplatin, the proteasome inhibitor MG-132 and the histone deacetylase inhibitor MS-275. Within the here used time-period (14 hr) genistein, alone or with ATO, did not significantly affect Akt phosphorylation and NF-,B binding activity, nor decreased intracellular GSH content. However, it elicited N -acetyl- L -cysteine-inhibitable phosphorylation of p38-MAPK and AMPK, and apoptosis was attenuated by pharmacologic inhibitors against these kinases. The pro-oxidant capacity of genistein might be exploited to improve the efficacy of ATO as anti-leukemic agent, and perhaps the efficacy of other oxidation-based therapeutic approaches. © 2008 Wiley-Liss, Inc. [source] Construction of self-cloning industrial brewing yeast with high-glutathione and low-diacetyl productionINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 6 2008Zhao-Yue Wang Summary Self-cloning strains of industrial brewing yeast were constructed, in which one allele of ,-acetohydroxyacid synthase (AHAS) gene (ILV2) was disrupted by integrating Saccharomyces cerevisiae genes, ,-glutamylcysteine synthetase gene (GSH1) and copper resistant gene (CUP1) into the locus of ILV2. The self-cloning strains were selected for their resistance to CuSO4 and identified by PCR amplification. The results of AHAS and glutathione (GSH) assay from fermentation with the self-cloning strains in 500-mL conical flask showed that AHAS activity decreased and GSH content increased compared with that of host yeasts. The results of pilot scale brewing in 5-L fermentation tank also indicated that GSH content in beer fermented with self-cloning strains T5-3 and T31-2 was 1.3 fold and 1.5 fold of that of host QY5 and QY31, respectively; and diacetyl content decreased to 64% and 58% of their hosts, respectively. The self-cloning strains do not contain any heterologous DNA, they may be more acceptable to the public. [source] Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous routeJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2006A. S. Kulkarni Abstract Sulfur mustard (SM), chemically bis (2-chloroethyl) sulfide is a bifunctional alkylating agent that causes serious blisters on contact with human skin. Although several antidotes have been reported for the systemic toxicity of SM in experimental animals none of them are approved so far and decontamination of SM immediately by physical or chemical means is recommended as the best protection. Two compounds amifostine [S-2(3-aminopropylamino) ethyl phosphorothioate] and DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulfide] gave very good protection as an oral prophylactic agent against SM the in mouse model, but in the rat model the protection was only moderate. In the search for more effective and less toxic compounds, a number of analogues of DRDE-07 were synthesised and their protective efficacy was evaluated in mouse and rat models. The LD50 of S-aryl substitution was between 1 and 2 g kg,1 and S-alkyl substitution was more than 2 g kg,1. In the mouse model, DRDE-07, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 gave about 20 fold protection, and DRDE-23 and DRDE-38 gave less protection of 4.8 and 9.0 fold respectively, against percutaneously administered SM. In the rat model, DRDE-07, DRDE-09, DRDE-10 and DRDE-21 gave about two fold protection. Percutaneously administered SM (19.33 mg kg,1) significantly depleted the hepatic GSH content in mice. Pretreatment with DRDE-21 significantly elevated the levels. A 4.4 fold increase in % DNA fragmentation was observed 7 days after SM administration (19.33 mg kg,1) in mice. Pretreatment with DRDE-07, DRDE-09, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 significantly protected the mice from SM induced DNA damage. The histopathological lesions in liver and spleen induced by percutaneously administered SM was reduced by pretreatment with DRDE-07, DRDE-09, DRDE-10 and DRDE-21. These analogues may prove as prototypes for the designing of more effective prophylactic drug for SM. Copyright © 2006 John Wiley & Sons, Ltd. [source] REDUCED/OXIDIZED GLUTATHIONE INDEX AS A TOOL FOR FOOD MONITORITY OXIDATIVE STRESS DURING EXTRUSION COOKINGJOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 3 2001H. ZIELINSKI Reduced and oxidized glutathione was assayed in wheat, barley, rye, oats and buckwheat before and after extrusion cooking. The results obtained indicate that GSH/GSSG ratio was decreased from 1.91 and 10.72 for raw oat and buckwheat grains to the 1.13, 1.01, 1.10 and 4.72, 3.89, 3.89 for extruded material, respectively, in temperature used of 120, 160 and 200C. These results indicate that the oxidative stress is least developed during extrusion cooking of oat and buckwheat grains. Wheat and barley grains were more prone to oxidative damage, and the observed decrease of the ratio ranged from 6.84 and 4.89 (wheat cv. Almari and barley cv. Mobek, raw material) to the 1.89 and 2.07 (after extrusion cooking at 200C, respectively). No significance differences were found between two cultivars of wheat and barley being used in the experiment. The most decreased ratio up to five times was found in rye grain extrudates. The extrusion performed under barrel temperature profile of 80,100,120,120,120C caused significant decrease in GSH content when compared to raw material. The next higher barrel temperature profiles of 100,130,160,160,120C and 120,160,200,200,120C led to further GSH decrease in extruded wheat grains. In contrast, the two high temperature profiles did not [source] The effect of sildenafil, a phosphodiesterase-5 inhibitor, on acetic acid-induced colonic inflammation in the ratJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2009Sevgin Ozlem Iseri Abstract Background and Aim:, Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid-induced colitis. Methods:, Colitis was induced by intrarectal administration of 1 mL of 5% acetic acid to Sprague-Dawley rats (200,250 g; n = 7,8/group). Control rats received an equal volume of saline intrarectally. In treatment groups, the rats were treated with either sildenafil citrate (5 mg/kg/day; subcutaneously) or saline for 3 days. After decapitation, distal colon was weighed and scored macroscopically and microscopically. Tissue samples were used for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and oxidant production. Trunk blood was collected for the assessment of serum tumor necrosis factor (TNF)-, and interleukin (IL)-1, levels. Results:, In the colitis group, the colonic tissue was characterized by lesions, increased lipid peroxidation with a concomitant reduction in GSH content, increased MPO activity and oxidant production. Serum TNF-, and IL-1, levels were higher in the colitis group compared to control values. Sildenafil reversed these inflammatory parameters nearly back to control values. Conclusions:, Sildenafil citrate administration to rats with acetic acid-induced colitis seems to be beneficial via prevention of lipid peroxidation, oxidant generation, cytokine production and neutrophil accumulation. [source] Effect of endotoxin pretreatment on hepatic stellate cell response to ethanol and acetaldehydeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2001Silvia C Quiroz Abstract Background and Aim: The role of endotoxin in alcohol-induced liver damage is well recognized. How pre-exposure to endotoxin might affect alcohol injury is not known. We herein studied the effect of endotoxin pretreatment on hepatic stellate cell (HSC) response to ethanol and acetaldehyde. Methods: Rat HSC (CFSC-2G) were exposed to media supplemented with 1 ,g/mL lipopolysaccharide (LPS). This was followed by a 24 h exposure to media containing LPS plus 50 mmol/L ethanol or 175 ,mol/L acetaldehyde. Lipid peroxidation, collagen, and tumor necrosis factor (TNF)-,, interleukin (IL)-1,, IL-6 and transforming growth factor (TGF)-,1 secretion were determined at the end of both periods of exposure. Results: Lipopolysaccharide pretreatment did not modify lipid peroxidation induced by ethanol or acetaldehyde alone. Glutathione (GSH) content decreased to 4.2 ± 0.5 and 16.3 ± 0.8 nmol protein after exposure to ethanol or acetaldehyde alone, and decreased further with LPS pretreatment (2.4 ± 0.2 and 2.7 ± 0.3 nmol/mg protein, respectively). Oxidized GSH (GSSG) content increased in ethanol and acetaldehyde LPS-pretreated cells only. Collagen secretion increased to 988 ± 82 and 1169 ± 91 ,g/106 cells after exposure to acetaldehyde or LPS alone. Lipopolysaccharide pretreatment enhanced collagen secretion significantly in both ethanol- and acetaldehyde-treated cells (969 ± 56 and 1360 ± 72 ,g/106 cells, respectively). Interleukin-6 production increased to 288 ± 48, 1195 ± 86 and 247 ± 35 pg/mL per 106 cells after ethanol, acetaldehyde and LPS exposure, and increased further with LPS pretreatment in ethanol-exposed cells (680 ± 23 pg/mL 106 cells). Conclusion: Lipopolysaccharide pretreatment of HSC adds to the damage produced by ethanol and acetaldehyde by diminishing GSH content and increasing GSSG content, collagen and IL-6 secretion. [source] Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidencesJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Muzamil Ahmad Abstract Ginkgo biloba extract (EGb), a potent antioxidant and monoamine oxidase B (MAO-B) inhibitor, was evaluated for its anti-parkinsonian effects in a 6-hydroxydopamine (6-OHDA) rat model of the disease. Rats were treated with 50, 100, and 150 mg/kg EGb for 3 weeks. On day 21, 2 µL 6-OHDA (10 µg in 0.1% ascorbic acid saline) was injected into the right striatum, while the sham-operated group received 2 µL of vehicle. Three weeks after 6-OHDA injection, rats were tested for rotational behaviour, locomotor activity, and muscular coordination. After 6 weeks, they were killed to estimate the generation of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content, to measure activities of glutathione- S -transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and to quantify catecholamines, dopamine (DA) D2 receptor binding, and tyrosine hydroxylase-immunoreactive (TH-IR) fibre density. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by EGb. The lesion was followed by an increased generation of TBARS and significant depletion of GSH content in substantia nigra, which was gradually restored with EGb treatment. EGb also dose-dependently restored the activities of glutathione-dependent enzymes, catalase, and SOD in striatum, which had reduced significantly by lesioning. A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment. Finally, all of these results were exhibited by an increase in the density of TH-IR fibers in the ipsilateral substantia nigra of the lesioned group following treatment with EGb; the lesioning had induced almost a complete loss of TH-IR fibers. Considering our behavioural studies, biochemical analysis, and immunohistochemical observation, we conclude that EGb can be used as a therapeutic approach to check the neuronal loss following parkinsonism. [source] Thyroid hormone stimulates ,-glutamyl transpeptidase in the developing rat cerebra and in astroglial culturesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Asmita Dasgupta Abstract Hypothyroidism in the developing rat brain is associated with enhanced oxidative stress, one of the earliest manifestations of which is a decline in the level of glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH homeostasis, the effect of TH on ,-glutamyl transpeptidase (,GT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral ,GT at all postnatal ages examined (postnatal day 1,20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal injection of TH to 15-day-old rat pups increased the specific activity of ,GT by 25-30% within 4,6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of ,GT by 30,40% within 4,6 hr. The induction of ,GT by TH was blocked by actinomycin D or cycloheximide. ,GT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the ,GT-inhibitor, acivicin, GSH released in the culture medium of astrocytes increased linearly for at least 6 hr and TH had no effect on this accumulation pattern. In the absence of acivicin, GSH content of the medium from TH-treated cells was significantly lower than that of untreated controls due to activation of ,GT by TH and a faster processing of GSH. Because the products of ,GT reaction are putative precursors for neuronal GSH, the activation of ,GT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress. © 2005 Wiley-Liss, Inc. [source] Gender differences in glutathione metabolism in Alzheimer's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Honglei Liu Abstract The mechanism underlying Alzheimer's disease (AD), an age-related neurodegenerative disease, is still an area of significant controversy. Oxidative damage of macromolecules has been suggested to play an important role in the development of AD; however, the underlying mechanism is still unclear. In this study, we showed that the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, was decreased in red blood cells from male AD patients compared with age- and gender-matched controls. However, there was no difference in blood GSH concentration between the female patients and female controls. The decrease in GSH content in red blood cells from male AD patients was associated with reduced activities of glutamate cysteine ligase and glutathione synthase, the two enzymes involved in de novo GSH synthesis, with no change in the amount of oxidized glutathione or the activity of glutathione reductase, suggesting that a decreased de novo GSH synthetic capacity is responsible for the decline in GSH content in AD. These results showed for the first time that GSH metabolism was regulated differently in male and female AD patients. © 2005 Wiley-Liss, Inc. [source] Lipid Peroxidation and Antioxidant Activities Involved in Resistance Response against Downy Mildew in Opium PoppyJOURNAL OF PHYTOPATHOLOGY, Issue 2 2010Mukesh K. Dubey Abstract The aim of this study was to observe the lipid peroxidation (LP) of cell membranes and antioxidant systems in response to inoculation of Peronospora arborescens causing downy mildew (DM) in opium poppy. Contents of the LP product, malondialdehyde (MDA) and antioxidant glutathione (GSH) were determined in leaves of two opium poppy genotypes, Pps-1 (highly resistant to DM) and Jawahar-16 (highly susceptible to DM) at different time intervals after inoculation (12 h, 24 h, 48 h and 72 h). The provided GSH content corresponded to that of total non-protein sulfhydryl groups. In leaves of Jawahar-16, a significant decrease in concentration of GSH and a persistent increase in concentration of MDA were recorded after inoculation in comparison to leaves of control plants. The continuous decrease in GSH content contributed to damage of cell membranes leading to disease development in Jawahar-16. On the other hand in a resistant genotype (Pps-1), initially at 12 h after inoculation (hai) the level of GSH was found to be high, but a transient and highly significant decrease in content of GSH and increase in content of MDA was observed at 24 hai in comparison to control plants of same genotype and also in comparison to inoculated plants of susceptible genotype (Jawahar-16). These results indicate that generation of GSH and MDA is negatively correlated during the infection process as found in the case of DM-resistant genotype Pps-1 at 24hai, which also suggests an increased need by the host plant for oxidative stress, required for hypersensitive response mediated defense mechanism. [source] Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptomsJOURNAL OF PINEAL RESEARCH, Issue 3 2009Mehmet Ersahin Abstract:, Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood,brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+ -K+ -ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+ -K+ -ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema. [source] Enhanced glutathione production by using low-pH stress coupled with cysteine addition in the treatment of high cell density culture of Candida utilisLETTERS IN APPLIED MICROBIOLOGY, Issue 5 2008G. Liang Abstract Aims:, To investigate the effects of pH stress coupled with cysteine addition on glutathione (GSH) production in the treatment of high cell density culture of Candida utilis. Methods and Results:, We have previously observed that most Candida utilis cells remained viable after being subjected to pH at 1·2 for 3 h and that some intracellular GSH leaked into the medium. A cysteine addition strategy was applied in fed-batch production of GSH. A single cysteine addition resulted in higher GSH yield than two separate additions without pH stress. An increase in intracellular GSH content triggered inhibition of ,-glutamylcysteine synthetase (,-GCS). A strategy that combines cysteine addition with low-pH stress was developed to relieve the inhibition of ,-GCS. Conclusion:, Without pH stress, single shot and double shot cysteine addition yielded a total GSH of 1423 and 1325 mg l,1. In comparison, a low-pH stress counterpart resulted in a total GSH of 1542 and 1730 mg l,1, respectively. With low-pH stress, we observed GSH secretion into the medium at 673 and 558 mg l,1 and an increase in the ,-GCS activity by 1·2- and 1·5-fold, respectively. The specific GSH production yield increased from 1·76% to 1·91% (w/w) for single shot, and 1·64% to 2·14% for double shots. Significance and Impact of the Study:, Low-pH shift was applied to alleviate the feedback inhibition of intracellular GSH on ,-GCS activity by secreting GSH into the medium. This strategy is coupled with cysteine addition to enhance GSH production in Candida utilis. [source] ,-Glucuronidase inhibitor tectorigenin isolated from the flower of Pueraria thunbergiana protects carbon tetrachloride-induced liver injuryLIVER INTERNATIONAL, Issue 4 2003Hae-Woong Lee Abstract Background/Aim: To understand the relationship between the fluctuation in serum ,-glucuronidase and hepatotoxicity, an inhibitor of ,-glucuronidase was isolated from the flowers of Pueraria thunbergiana and its hepatoprotective activity was measured. Method: Tectorigenin was isolated from the flowers of pueria thunbergiana as an inhibitor of ,-glucuronidase, and serum ALT, AST and biological parameters as markers for its hepatoprotective activity were measured on CCl4 -induced liver injury in mice. The relationship between serum ,-glucuronidase and hepatoprotective activities in mice was measured. Results: When tectorigenin at a dose of 100 mg/kg was intraperitoneally administered on CCl4 -induced liver injury in mice, it significantly inhibited the increase of plasma ALT, AST and LDH activities. The inhibitory effect of tectorigenin is much more potent than that of dimethyl diphenyl bicarboxylate (DDB), which has been used as a commercial hepatoprotective agent. When tectoridin transformed to tectorigenin by intestinal bacteria was orally administered to mice, it showed hepatoprotective activity. However, when tectoridin was intraperitoneally administrated to mice, it did not exhibit hepatoprotective activity. Moreover, orally administered tectoridin not only inhibited ,-glucuronidase but also increased GSH content and GST activity on CCl4 -induced hepatotoxicity of mice. Conclusion: We insist that an inhibitor of ,-glucuronidase tectorigenin may be hepatoprotective and tectoridin should be a prodrug transformed to tectorigenin. [source] Glutathione and adenosine triphosphate content of in vivo and in vitro matured porcine oocytesMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2003A.M. Brad Abstract Glutathione (GSH) content in mature porcine oocytes is correlated with subsequent fertilization and developmental success. Adenosine triphosphate (ATP) is an important energy source for maintaining cellular activities and protein synthesis. The objective of this study was to compare GSH and ATP concentrations of in vivo and in vitro matured porcine oocytes. Ovulated, in vivo matured oocytes were frozen at ,80°C in groups of 10,20 (GSH) or 5,10 (ATP). In vitro oocytes were matured in either tissue culture medium-199 (TCM199) supplemented with polyvinyl alcohol (PVA) or hyaluronic acid (MAP5), or North Carolina State University-23 (NCSU23) supplemented with porcine follicular fluid (pFF) and frozen as described, or fertilized and cultured. GSH content was determined by the dithionitrobenzoic acid,glutathione disulfide (DTNB,GSSG) reductase recycling assay. ATP content was determined by using the Bioluminescent Somatic Cell Assay Kit. Oocytes matured in vitro in defined TCM199 with PVA or hyaluronic acid, or NCSU23 with pFF had significantly lower concentrations (P,<,0.05) of GSH (n,=,207, 9.82,±,0.71 pmol/oocyte; n,=,104, 9.73,±, 0.81 pmol/oocyte; n,=,108, 7.89,±,0.66 pmol/oocyte, respectively) compared to in vivo matured oocytes (n,=,217, 36.26,±,11.00 pmol/oocyte). Concentrations of ATP were not different between treatments (in vivo, n,=,70, 0.97,±,0.07 pmol/oocyte; TCM,PVA, n,=,117, 0.81,±,0.13 pmol/oocyte; TCM,MAP, n,=,107, 1.02,±,0.18 pmol/oocyte; NCSU,pFF, n,=,134, 0.71,±,0.08 pmol/oocyte). Intracellular ATP content does not appear to be related to developmental potential in porcine oocytes. Low intracellular GSH may be responsible, in part, for lower developmental competence observed in in vitro matured porcine oocytes. Mol. Reprod. Dev. 64: 492,498, 2003. © 2003 Wiley-Liss, Inc. [source] Importance of glutathione in the nodulation process of peanut (Arachis hypogaea)PHYSIOLOGIA PLANTARUM, Issue 2 2008Eliana Bianucci GSH appears to be essential for proper development of the root nodules during the symbiotic association of legume,rhizobia in which the entry of rhizobia involves the formation of infection threads. In the particular case of peanut,rhizobia symbiosis, the entry of rhizobia occurs by the mechanism of infection called ,crack entry', i.e. entry at the point of emergence of lateral roots. We have previously shown the role of GSH content of Bradyrhizobium sp. SEMIA 6144 during the symbiotic association with peanut using a GSH-deficient mutant obtained by disruption of the gshA gene, encoding ,-glutamylcysteine synthetase (,-GCS), which was able to induce nodules in peanut roots without alterations in the symbiotic phenotype. To investigate the role of the peanut GSH content in the symbiosis, the compound l -buthionine-sulfoximine (BSO), a specific inhibitor of ,-GCS in plants, was used. There were no differences in the plant growth and the typical anatomic structure of the peanut roots when the plants grew in the Fahraeus medium either in presence or in absence of 0.1 mM BSO. However, the GSH content was reduced by 51% after treatment with BSO. The BSO-treated plants inoculated with wild-type or mutant strains of Bradyrhizobium sp. showed a significant reduction in the number and dry weight of nodules, suggesting that GSH content could play an important role in the nodulation process of root peanut with Bradyrhizobium sp. [source] Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague-dawley ratsPHYTOTHERAPY RESEARCH, Issue 9 2010Chung Mu Park Abstract The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2,g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5,mL/kg bw) was administered 24,h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4 -induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-? mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4 -induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4. Copyright © 2010 John Wiley & Sons, Ltd. [source] Azadirachta indica modulates carcinogen biotransformation and reduced glutathione at peri-initiation phase of benzo(a)pyrene induced murine forestomach tumorigenesisPHYTOTHERAPY RESEARCH, Issue 9 2008Subhash Chander Gangar Abstract The present study evaluated the effects of aqueous Azadirachta indica leaf extract (AAILE) on the activities of certain phase I (cytochrome P450, cytochrome b5 and aryl hydrocarbon hydroxylase) as well as phase II (glutathione- S -transferase and UDP-glucuronosyl transferase) biotransformation enzymes; and reduced glutathione (GSH) (in forestomach and hepatic tissues) during/after intra-gastric instillations of B(a)P in murine forestomach tumorigenesis bioassay protocol. The activities of phase I biotransformation enzymes were found to increase, whereas a decrease in GSH content as well as glutathione- S -transferase was observed in mice receiving only B(a)P during as well as 2 weeks after B(a)P instillations. The activity of UDP-glucuronosyltransferase decreased during B(a)P instillations, whereas after the latter, the activity increased when compared with the control mice. However, in mice that received AAILE along with B(a)P instillations, a decrease in phase I enzymes was accompanied by an increase in phase II enzymes as well as GSH contents. Only AAILE treatment reduced the activities of phase I biotransformation enzymes and enhanced the GSH contents as well as the activities of phase II enzymes. Observations of the present study seem to be quite significant and (when taken together with our earlier findings) provides evidence for A. indica mediated modulation of the peri-initiation phase of the process of forestomach tumorigenesis. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effect of parsley (Petroselinum crispum (Mill.) Nym. ex A.W. Hill, Apiaceae) extracts on some biochemical parameters of oxidative stress in mice treated with CCl4PHYTOTHERAPY RESEARCH, Issue 8 2007Mira Popovi Abstract The in vitro and in vivo antioxidant activity of different extracts of leaves and root of parsley (Petroselinum crispum (Mill.) Nym. ex A.W. Hill, Apiaceae) were studied. Free radical scavenging capacity (RSC) was evaluated measuring the scavenging activity on the 2,2-diphenyl-1-picrylhydrazil (DPPH) and OH radicals. Also, the effects on lipid peroxidation (LP) were evaluated. The results obtained showed that all examined extracts act as good scavengers of DPPH and OH radicals and reduce the intensity of LP. The in vivo effects were evaluated on some antioxidant systems (activities of LPx, GSH-Px, Px, CAT and XOD, and GSH content) in the mice liver and blood after treatment with the examined parsley extracts, or in combination with carbon tetrachloride (CCl4). On the basis of the results obtained it can be concluded that the examined extracts exhibited a certain protective effect. However, combined treatments with CCl4 and the examined extracts showed both positive and negative synergism, inducing or suppressing the influence of CCl4 alone. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effect of celery (Apium graveolens) extracts on some biochemical parameters of oxidative Stress in mice treated with carbon tetrachloridePHYTOTHERAPY RESEARCH, Issue 7 2006Mira Popovi Abstract Extracts of celery leaves and roots in ether, chloroform, ethyl acetate, n -butanol and water were evaporated to dryness and dissolved in 50% ethanol to make 10% (w[sol ]v) solutions. The potential protective action of the extracts was assessed by the corresponding in vitro and in vivo tests. In the in vitro experiments crude methanol extracts were tested as potential scavengers of free OH, and DPPH, radicals, as well as inhibitors of liposomal peroxidation (LPx). Analogous experiments were also carried out with the extracts of celery root, for comparison. The results obtained show that both the extracts of root and leaves are good scavengers of OH, and DPPH, radicals and reduce LPx intensity in liposomes, which points to their protective (antioxidant) activity. In vivo experiments were concerned with antioxidant systems (activities of GSHPx, GSHR, Px, CAT, XOD, GSH content and intensity of LPx) in liver homogenate and blood of mice after their treatment with extracts of celery leaves, or in combination with CCl4. On the basis of the results obtained it can be concluded that the examined extracts showed a certain protective effect. Of all the extracts the n -butanol extract showed the highest protective effect. Combined treatments with CCl4 and extracts showed both positive and negative synergism , inducing or suppressing the impact of CCl4 alone. The differences observed in the action of particular extracts are probably due to the different contents of flavonoids and some other antioxidant compounds. Copyright © 2006 John Wiley & Sons, Ltd. [source] Whole Plant Regulation of Sulfur Nutrition of Deciduous Trees-Influences of the EnvironmentPLANT BIOLOGY, Issue 3 2003C. Herschbach Abstract: The current view of sulfur nutrition is based on the source-to-sink relationship of carbohydrates. SO42- reduction is thought to occur mainly in leaves. Surplus reduced sulfur must be transported out of the leaves, loaded into the phloem and transported to other tissues, in particular tissues assumed to be sink organs. However, it has not been proved that tissues which are sinks for carbohydrates are also sink organs for reduced sulfur. It is evident that sinks must communicate with sources, and vice versa, to signal demand and to transport the surplus of reduced sulfur that is produced. The demand-driven control model of sulfur nutrition proposes that the tripeptide glutathione is the signal which regulates S nutrition of the whole plant at the level of SO42- uptake. Acclimatization to environmental changes has been shown to result in several changes in S nutrition of deciduous trees: (i) Drought stress diminished SO42- transport into the xylem, although the GSH content in lateral roots remained unaffected, possibly due to an overall reduction in water status. (ii) Flooding decreased APS reductase activity in the anoxic roots. This may be due to enhanced GSH transport to the roots, but it is more likely to be the result of a change in metabolism leading to diminished energy gain in the roots. (iii) Mycorrhization enhanced the GSH content in the phloem, while SO42- uptake was not affected. This clearly goes against the demand-driven control model. (iv) Under both short- and long-term exposure to elevated pCO2, the APS reductase activity in leaves and lateral roots did not correlate with the GSH contents therein. Therefore, it must be assumed that, under these conditions, regulation of S nutrition goes beyond the demand-driven control model, and occurs within the network of other nutrient metabolism. (v) Atmospheric S in the form of H2S enhanced the reduced sulfur content of the phloem and lateral roots. Under these conditions, the SO42- loaded into the xylem decreased. It would appear that the demand-driven control model of sulfur nutrition is not always valid in the case of deciduous trees. [source] Progression of Lipid Peroxidation Measured as Thiobarbituric Acid Reactive Substances, Damage to DNA and Histopathological Changes in the Liver of Rats Subjected to a Methionine,Choline-Deficient DietBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Alceu Afonso Jordao Male rats were divided into three groups, the first group receiving a control diet and the other two groups receiving a methionine,choline-deficient diet for 1 month (MCD1) and for 2 months (MCD2), respectively. The livers of the animals were collected for the determination of vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration, DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1 and MCD2) compared to control diet, and hepatic vitamin E concentration differed (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2 group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes). Liver histopathological evaluation showed that steatosis, present in experimental groups was micro- and macro-vesicular and concentrated around the centrolobular vein, zone 3, with preservation of the portal space. The inflammatory infiltrate was predominantly periductal and the steatosis and inflammatory infiltrate was similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was greater in the MCD2 group. The study describes the contribution of a methionine,choline-deficient diet to the progression of steatosis, lipid peroxidation and hepatic DNA damage in rats, serving as a point of reflection about the role of these nutrients in the western diet and the elevated non-alcoholic steatohepatitis rates in humans. [source] MRP1/GS-X pump ATPase expression: is this the explanation for the cytoprotection of the heart against oxidative stress-induced redox imbalance in comparison to skeletal muscle cells?CELL BIOCHEMISTRY AND FUNCTION, Issue 1 2007Maurício S. Krause Abstract Striated muscle activity is always accompanied by oxidative stress (OxStress): the more intense muscle work and/or its duration, the more a redox imbalance may be attained. In spite of cardiac muscle functioning continuously, it is well known that the heart does not suffer from OxStress-induced damage over a broad physiological range. Although the expression of antioxidant enzymes may be of importance in defending heart muscle against OxStress, a series of combined antioxidant therapeutic approaches have proved to be mostly ineffective in avoiding cellular injury. Hence, additional mechanisms may be involved in heart cytoprotection other than antioxidant enzyme activities. The strong cardiotoxic effect of doxorubicin-induced cancer chemotherapy shed light on the possible role for multidrug resistance-associated proteins (MRP) in this context. Muscle activity-induced ,physiological' OxStress enhances the production of glutathione disulfide (GSSG) thus increasing the ratio of GSSG to glutathione (GSH) content inside the cells, which, in turn, leads to redox imbalance. Since MRP1 gene product (a GS-X pump ATPase) is a physiological GSSG transporter, adult Wistar rats were tested for MRP1 expression and activity in the heart and skeletal muscle (gastrocnemius), in as much as the latter is known to be extremely sensitive to muscle activity-induced OxS. MRP1 expression was completely absent in skeletal muscle. In contrast, the heart showed an exercise training-dependent induction of MRP1 protein expression which was further augmented (2.4-fold) as trained rats were challenged with a session of acute exercise. On the other hand, inducible expression of the 70-kDa heat shock protein (HSP70), a universal marker of cellular stress, was completely absent in the heart of sedentary and acutely exercised rats, whereas skeletal muscle showed a conspicuous exercise-dependent HSP70 expression, which decreased by 45% with exercise training. This effect was paralleled by a 58% decrease in GSH content in skeletal muscle which was even higher (an 80%-fall) after training thus leading to a marked redox imbalance ([GSSG]/[GSH] raised up to 38-fold). In the heart, GSH contents and [GSSG]/[GSH] ratio remained virtually unchanged even after exercise challenges, while GS-X pump activity was found to be 20% higher in the heart related to skeletal muscle. These findings suggest that an intrinsic higher capacity to express the MRP1/GS-X pump may dictate the redox status in the heart muscle thus protecting myocardium by preventing GSSG accumulation in cardiomyocytes as compared to skeletal muscle fibres. Copyright © 2006 John Wiley & Sons, Ltd. [source] Oxidative stress on EAAC1 is involved in MPTP-induced glutathione depletion and motor dysfunctionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Koji Aoyama Abstract Excitatory amino acid carrier 1 (EAAC1) is a glutamate transporter expressed on mature neurons in the CNS, and is the primary route for uptake of the neuronal cysteine needed to produce glutathione (GSH). Parkinson's disease (PD) is a neurodegenerative disorder pathogenically related to oxidative stress and shows GSH depletion in the substantia nigra (SN). Herein, we report that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, an experimental model of PD, showed reduced motor activity, reduced GSH contents, EAAC1 translocation to the membrane and increased levels of nitrated EAAC1. These changes were reversed by pre-administration of n-acetylcysteine (NAC), a membrane-permeable cysteine precursor. Pretreatment with 7-nitroindazole, a specific neuronal nitric oxide synthase inhibitor, also prevented both GSH depletion and nitrotyrosine formation induced by MPTP. Pretreatment with hydrogen peroxide, l -aspartic acid ,-hydroxamate or 1-methyl-4-phenylpyridinium reduced the subsequent cysteine increase in midbrain slice cultures. Studies with chloromethylfluorescein diacetate, a GSH marker, demonstrated dopaminergic neurons in the SN to have increased GSH levels after NAC treatment. These findings suggest that oxidative stress induced by MPTP may reduce neuronal cysteine uptake, via EAAC1 dysfunction, leading to impaired GSH synthesis, and that NAC would exert a protective effect against MPTP neurotoxicity by maintaining GSH levels in dopaminergic neurons. [source] Cardiotoxicity of doxorubicin/paclitaxel combination in rats: Effect of sequence and timing of administrationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2004Sherif Y. Saad Abstract The higher incidence of cardiotoxicity of doxorubicin (DOX)/paclitaxel (PTX) combination compared with DOX alone remains to be a major obstacle against effective chemotherapeutic treatment. We investigated the effect of sequence and time interval between administration of both drugs on the severity of cardiotoxicity of the combination. Male Wistar rats were divided into seven groups. DOX was administeded intraperitoneally (ip) at a single dose of 5 mg kg,1 every other 2 days, 2 doses per week for a total cumulative dose of 20 mg kg,1. PTX was administered by an ip route at a dose of 20 mg kg,1 every other 2 days. Both drugs were injected either alone or sequentially in combination. In one case, DOX preceded PTX by 30 min and 24 h and in the other case, PTX preceded DOX by 30 min and 24 h. Cardiotoxicity was evaluated by both biochemical and histopathological examination, 48 h after the last DOX dose. DOX-induced cardiotoxicity was manifested by abnormal biochemical changes including marked increases in serum creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), and aspartate aminotransferase (AST) activity levels. Myocardial tissue from DOX-treated rats showed significant increases in malondialdehyde (MDA) production and total nitrate/nitrite (NOx) levels, parallel with depletion of "endogenous antioxidant reserve," including GSH contents and GSH-Px activity level. PTX treatment produced significant changes in the biochemical parameters measured by a lower magnitude than those changes produced by DOX alone. Combination of both drugs resulted in aggravation of DOX-induced cardiotoxicity regardless the sequence and time interval between administration of either drug. Administration of PTX 30 min and 24 h after DOX treatment showed exaggeration of combination-induced cardiotoxicity compared with the reverse sequence. This exacerbation was manifested by much more pronounced changes in serum and cardiac tissue parameters measured. Histopathological examination of ventricles of rat's heart revealed that DOX treatment produced myo-cytolysis and myocardial necrosis. Administration of PTX following DOX treatment showed extensive myocardial necrosis compared with those rats treated with either DOX alone or the reverse sequence of administration. Moreover, rats treated with PTX 24 h after DOX treatment showed exaggeration of the combination-induced cardiotoxicity. In conclusion, PTX might synergistically aggravate DOX-induced cardiotoxicity. The effect might be much more pronounced with those rats treated with PTX 24 h after DOX treatment. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:78,86, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20012 [source] Effect of sulforaphane on glutathione-adduct formation and on glutathione_S_transferase-dependent detoxification of acrylamide in Caco-2 cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 12 2009Rita Pernice Abstract The toxicity of dietary acrylamide (AA) depends on its biotransformation pathways, in which phase I cytochrome P-450 enzymes transform AA into glycidamide. The phase II enzyme glutathione_S_transferase (GST) catalyses the conjugation of AA with glutathione (GSH). GST induction by phytochemicals like sulforaphane (SFN) plays a role in chemoprevention. Here, the effect of SFN on the detoxification of AA through GSH conjugation was studied in Caco-2 cells. GSH adducts with AA and SFN were synthesized, identified by NMR and quantified by LC-MS/MS. Caco-2 cells were treated with either 2.5,mM AA, 10,,M SFN or the combination of both for 24,h. Concentrations of GSH conjugates (GSH-AA, GSH-SFN, SFN-GSH-AA), AA and SFN were analysed by LC-MS/MS. GSH contents and GST activity were determined photometrically. GST activity was increased after treatment of the cells with SFN (38±6%, p,0.05) or AA (25±4%, p,0.05). GSH concentrations decreased after all treatments. Quantitative data of GSH adduct formation showed that the reaction between GSH and SFN is favoured over that between GSH and AA. The data suggest that SFN might impair the GSH-dependent detoxification of AA by SFN-GSH adduct formation and, thus, lower the GSH concentrations available for its reaction with AA. [source] Azadirachta indica modulates carcinogen biotransformation and reduced glutathione at peri-initiation phase of benzo(a)pyrene induced murine forestomach tumorigenesisPHYTOTHERAPY RESEARCH, Issue 9 2008Subhash Chander Gangar Abstract The present study evaluated the effects of aqueous Azadirachta indica leaf extract (AAILE) on the activities of certain phase I (cytochrome P450, cytochrome b5 and aryl hydrocarbon hydroxylase) as well as phase II (glutathione- S -transferase and UDP-glucuronosyl transferase) biotransformation enzymes; and reduced glutathione (GSH) (in forestomach and hepatic tissues) during/after intra-gastric instillations of B(a)P in murine forestomach tumorigenesis bioassay protocol. The activities of phase I biotransformation enzymes were found to increase, whereas a decrease in GSH content as well as glutathione- S -transferase was observed in mice receiving only B(a)P during as well as 2 weeks after B(a)P instillations. The activity of UDP-glucuronosyltransferase decreased during B(a)P instillations, whereas after the latter, the activity increased when compared with the control mice. However, in mice that received AAILE along with B(a)P instillations, a decrease in phase I enzymes was accompanied by an increase in phase II enzymes as well as GSH contents. Only AAILE treatment reduced the activities of phase I biotransformation enzymes and enhanced the GSH contents as well as the activities of phase II enzymes. Observations of the present study seem to be quite significant and (when taken together with our earlier findings) provides evidence for A. indica mediated modulation of the peri-initiation phase of the process of forestomach tumorigenesis. Copyright © 2008 John Wiley & Sons, Ltd. [source] A combination of soy isoflavone supplementation and exercise improves lipid profiles and protects antioxidant defense-systems against exercise-induced oxidative stress in ovariectomized ratsBIOFACTORS, Issue 4 2007Hea Young Oh Abstract Menopause is often accompanied with weight gain, metabolic lipid abnormalities, and oxidative stress. In this study, we investigated the combined effects of exercise and soy isoflavone supplemention on the lipid profiles and antioxidant capacities of ovariectomized rats. Twenty-five female Sprague-Dawley rats were divided into 5 groups: sham-operated, ovariectomized (OVX), OVX with exercise (OVX + EX), OVX with soy isoflavone supplementation (OVX + ISO), and OVX with both soy isoflavones and exercise (OVX + ISO + EX). After 12 weeks of intervention, antioxidant status was evaluated in collected blood samples by the ferric reducing ability of plasma (FRAP), glutathione (GSH) content, and sodium oxide dismutase (SOD) activity. DNA damage in the lymphocytes was determined using alkaline single-cell gel electrophoresis (the Comet assay). Although there were no significant differences in weight gain and food intake, weight gain was lower in OVX + EX, OVX + ISO, and OVX + ISO + EX than in OVX. OVX + EX, OVX + ISO, and OVX + ISO + EX showed a significant decrease in total cholesterol, triglycerides, and LDL-cholesterol compared to OVX. The soy isoflavone supplemented group had significantly increased FRAP values and GSH contents in contrast to no changes in the exercised group, whereas exercise markedly increased SOD activity and H2O2 -induced DNA tail length and tail moment. Exercise with soy isoflavone supplementation significantly increased FRAP values and had no difference on SOD activity, including DNA damage. These results demonstrate that a combined treatment of moderate exercise and soy isoflavone supplementation could exert a beneficial effect on weight control and lipid profiles, and offer protection from exercise-induced oxidative stress in postmenopausal women. [source] MRP1/GS-X pump ATPase expression: is this the explanation for the cytoprotection of the heart against oxidative stress-induced redox imbalance in comparison to skeletal muscle cells?CELL BIOCHEMISTRY AND FUNCTION, Issue 1 2007Maurício S. Krause Abstract Striated muscle activity is always accompanied by oxidative stress (OxStress): the more intense muscle work and/or its duration, the more a redox imbalance may be attained. In spite of cardiac muscle functioning continuously, it is well known that the heart does not suffer from OxStress-induced damage over a broad physiological range. Although the expression of antioxidant enzymes may be of importance in defending heart muscle against OxStress, a series of combined antioxidant therapeutic approaches have proved to be mostly ineffective in avoiding cellular injury. Hence, additional mechanisms may be involved in heart cytoprotection other than antioxidant enzyme activities. The strong cardiotoxic effect of doxorubicin-induced cancer chemotherapy shed light on the possible role for multidrug resistance-associated proteins (MRP) in this context. Muscle activity-induced ,physiological' OxStress enhances the production of glutathione disulfide (GSSG) thus increasing the ratio of GSSG to glutathione (GSH) content inside the cells, which, in turn, leads to redox imbalance. Since MRP1 gene product (a GS-X pump ATPase) is a physiological GSSG transporter, adult Wistar rats were tested for MRP1 expression and activity in the heart and skeletal muscle (gastrocnemius), in as much as the latter is known to be extremely sensitive to muscle activity-induced OxS. MRP1 expression was completely absent in skeletal muscle. In contrast, the heart showed an exercise training-dependent induction of MRP1 protein expression which was further augmented (2.4-fold) as trained rats were challenged with a session of acute exercise. On the other hand, inducible expression of the 70-kDa heat shock protein (HSP70), a universal marker of cellular stress, was completely absent in the heart of sedentary and acutely exercised rats, whereas skeletal muscle showed a conspicuous exercise-dependent HSP70 expression, which decreased by 45% with exercise training. This effect was paralleled by a 58% decrease in GSH content in skeletal muscle which was even higher (an 80%-fall) after training thus leading to a marked redox imbalance ([GSSG]/[GSH] raised up to 38-fold). In the heart, GSH contents and [GSSG]/[GSH] ratio remained virtually unchanged even after exercise challenges, while GS-X pump activity was found to be 20% higher in the heart related to skeletal muscle. These findings suggest that an intrinsic higher capacity to express the MRP1/GS-X pump may dictate the redox status in the heart muscle thus protecting myocardium by preventing GSSG accumulation in cardiomyocytes as compared to skeletal muscle fibres. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||