The effect of glutathione on glucosinolate biosynthesis through the sulfur assimilation pathway in pakchoi associated with the growth conditions

Glucosinolates(GSLs) are a group of nitrogen-and sulfur-containing secondary metabolites, synthesized primarily in members of the Brassicaceae family, that play an important role in food flavor, plant antimicrobial activity, resistance to insect attack, stress tolerance, and human anti-cancer effects. As a sulfur-containing compound, glutathione has a strong connection with GSLs biosynthesis as a sulfur donor or redox system, and exists in reduced(glutathione;GSH) and oxidized(glutathione disulfide;GSSG) forms. However, the mechanism of GSH regulating GSLs biosynthesis remainds unclear. Hence, the exogenous therapy to pakchoi under normal growth condition and sulfur deficiency condition were conducted in this work to explore the relevant mechanism. The results showed that exogenous application of buthionine sulfoximine, an inhibitor of GSH synthesis, decreased the transcript levels of GSLs synthesis-related genes and transcription factors, as well as sulfur assimilation-related genes under the normal growth condition. Application of exogenous GSH inhibited the expression of GSLs synthesis-and sulfur assimilation-related genes under the normal condition, while the GSLs biosynthesis and the sulfur assimilation pathway were activated by exogenous application of GSH when the content of GSH in vivo of plants decreased owing to sulfur deficiency. Moreover,exogenous application of GSSG increased the transcript levels of GSLs synthesis-and sulfur assimilation-related genes under the normal growth condition and under sulfur deficiency. The present work provides new insights into the molecular mechanisms of GSLs biosynthesis underlying glutathione regulation.

Plasma glutathione and oxidized glutathione level, glutathione/oxidized glutathione ratio, and albumin concentration in complicated and uncomplicated falciparum malaria

Objective: To compare the level of glutathione(GSH) and oxidized glutathione(GSSG),the ratio of GSH/GSSG and the concentration of albumin in plasma of patients with complicated and un-complicated falciparum malaria.Methods: This research was a cross sectional study using comparison analysis with the plasma GSH and GSSG, the ratio of plasma GSH/GSSG and the concentration of plasma albumin as variables. The complicated malaria patients were obtained from Dr. Saiful Anwar Hospital Malang, whereas uncomplicated malaria patients were obtained from the Regency of Pleihari South Kalimantan. Plasma GSH and GSSG levels were determined by the spectrophotometer at the wave length of 412 nm, whereas the concentration of albumin was determined by bromocresol green method in the p H of 4.1.Results: There were no significant differences between the level of plasma GSH and GSSG in complicated and uncomplicated malaria patients, as well as the ratio of plasma GSH/GSSG in the two groups(P = 0.373; P = 0.538; and P = 0.615, respectively, independent ttest). In contrast, the plasma albumin concentration in complicated malaria patients were significantly higher than uncomplicated malaria patients(P = 0.000, Mann Whitney U test).Conclusions: It can be concluded that the average of plasma GSH and GSSG level, also plasma GSH/GSSG ratio in complicated malaria are not different from uncomplicated malaria. Although plasma concentration of albumin in both groups is below the normal range,there is an increase in complicated malaria that might be as compensation of oxidative stress.

Increased oxidative damage of sperm and seminal plasma in men with idiopathic infertility is higher in patients with glutathione S-transferase Mu-1 null genotype

Aim： To examine whether a relationship exists between glutathione S-transferase Mu-1 （GSTM1） gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidative stress. Methods： Fifty-two men with idiopathic infertility and 60 healthy fertile men were recruited to this study. GSTM1 gene polymorphism was determined by polymerase chain reaction （PCR） and both the infertile and control individuals were divided into GSTM1 null and GSTM1 positive groups according to their GSTM1 gene structure. We compared reactive oxygen species （ROS） generation, malondialdehyde （MDA）, protein carbonyls and glutathione （GSH） concentrations, and glutathione S-transferase （GST） activity in seminal plasma and spermatozoa from infertile patients and controls with respect to GSTM1 genotype. Results： Significantly higher levels of oxidative stress and damage markers were found in idiopathic infertile men with the GSTM1 null genotype compared with those with the GSTM1 positive genotype. There was no significant difference in genotype distribution for theGSTM1 variant between the idiopathic infertile subjects and fertile subjects. Patients with the GSTM1 null genotype also had lower sperm concentrations than those with GSTM1 positive genotype. Conclusion： Our results suggest that the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype compared with those possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1 polymorphism might be an important source of variation in susceptibility of spermatozoa to oxidative damage.

Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress

AIM To determine whether oral glutathione(GSH)administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa. METHODS Rats were divided into eight groups.One group was fed ad libitum,another was fed ad libitum and received oral GSH,and six groups were administrated saline(SA)or GSH orally during fasting.Mucosal height,apoptosis,and cell proliferation in the jejunum were histologically evaluated.i NOS protein expression(by immunohistochemistry),nitrite levels(by high performance liquid chromatography,as a measure of NO production),8-hydroxydeoxyguanosine formation(by ELISA,indicating ROS levels),glutathione/oxidized glutathione(GSH/GSSG)ratio(by enzymatic colorimetric detection),andγ-glutamyl transpeptidase(Ggt1)mR NA levels in the jejunum(by semi-quantitative RT-PCR)were also estimated. RESULTS O r a l G S H a d m i n i s t r a t i o n w a s d e m o n s t r a t e d t o drastically reduce fasting-induced intestinal atrophy in the jejunum.In particular,jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals[527.2±6.9 for 50 mg/kg GSH,567.6±5.4 for 500 mg/kg GSH vs 483.1±4.9(μm),P<0.01at 72 h].This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iN OS protein staining[0.337±0.016for 50 mg/kg GSH,0.317±0.017 for 500 mg/kg GSH vs 0.430±0.023(area of staining part/area of tissue),P<0.01 at 72 h]and NO[2.99±0.29 for 50 mg/kg GSH,2.88±0.19 for 500 mg/kg GSH vs 5.34±0.35(nmol/g tissue),P<0.01 at 72 h]and ROS[3.92±0.46for 50 mg/kg GSH,4.58±0.29 for 500 mg/kg GSH vs6.42±0.52(8-OHdG pg/μg DNA),P<0.01,P<0.05at 72 h,respectively]levels as apoptosis mediators in the jejunum.Furthermore,oral GSH administration attenuated cell proliferation decreases in the fasting jejunum[182.5±1.9 for 500 mg/kg GSH vs 155.8±3.4(5-Brd U positive cells/10 crypts),P<0.01 at 72h].Notably,both GSH concentration and Ggt1 m RNA expression in the jejunum were also attenuated in rats following oral administration of GSH during fasting as compared with fasting alone[0.45±0.12 vs 0.97±0.06(nmol/mg tissue),P<0.01;1.01±0.11 vs 2.79±0.39(Ggt1 m RNA/Gapdh m RNA),P<0.01 for 500 mg/kg GSH at 48 h,respectively]. CONCLUSION Oral GSH administration during fasting enhances jejunal regenerative potential to minimize intestinal mucosal atrophy by diminishing fasting-mediated ROS generation and enterocyte apoptosis and enhancing cell proliferation.

Study of Oxidation of Glutathione by Capillary Electrophoresis

A capillary electrophoresis method for the separation and quantification of reduced glutathione (GSH) and oxidized glutathione (GSSG) was developed. A baseline separation was achieved within five minutes. The effects of time and the concentrations of hydrogen peroxide (H2O2) on the oxidation of GSH were investigated.

Glutathione peroxidase, superoxide dismutase and catalase activities in children with chronic hepatitis

The advantages of measuring hepatic oxidative status in liver biopsy are that it helps in diagnosis of hepatic dysfunction, reflects the degree of deterioration in the liver tissues, and helps to determine the severity of hepatic injury. We aimed to study the oxidative stress state in children with chronic hepatitis by using indirect approach in which antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) are determined in the liver tissue. The present study included 21 children and adolescents (12 males, 9 females) suffering from chronic hepatitis. Patients were selected from the Hepatology Clinic, New Children’s Hospital, Cairo University from November 2006 till 2009 and compared with a group of 7 children who happened to have incidental normal liver biopsy. Children with chronic hepatitis had mean age 8.12 ± 1.15 years. It was further subdivided into 2 subgroups: chronic viral heaptitis (n = 13) and cryptogenic hepatitis (n = 8). GPX, SOD and CAT levels were measured in fresh liver tissue (cell free homogenates) using ELISA. In chronic hepatitis group;there was a significant increase in the hepatic GPX activity (38.59 ± 35.82 nmol/min/ml) as compared to the control group (10.62 ± 6.68 nmol/min/ml). Also a significant correlation was observed between SOD and both ALT (r = 0.87, p < 0.05) and AST (r = 0.74, p < 0.05). GPX correlated with ALT (r = 0.80, p < 0.05) level in the chronic viral hepatitis subgroup. Our findings suggest that oxidative stress could play a role in the pathogenesis of chronic hepatitis. These preliminary results are encouraging to conduct more extensive clinical studies combining antioxidant therapy with various treatments.

Integrative Modeling of Oxidative Stress and C1 Metabolism Reveals Upregulation of Formaldehyde and Downregulation of Glutathione

This research provides, to the authors’ knowledge, the first integrative model of oxidative stress and C1 metabolism in plants. Increased oxidative stress can cause irreversible damage to photosynthetic components and is harmful to plants. Perturbations at the genetic level may increase oxidative stress and upregulate antioxidant systems in plants. One of the key mechanisms involved in oxidative stress regulation is the ascorbate-glutathione cycle which operates in chloroplasts as well as the mitochondria and is responsible for removal of reactive oxygen species (ROS) generated during photosynthetic operations and respiration. In this research, the complexity of molecular pathway systems of oxidative stress is modeled and then integrated with a previously developed in silico model of C1 metabolism system. This molecular systems integration provides two important results: 1) demonstration of the scalability of the CytoSolve&#174?Collaboratory&#153, a computational systems biology platform that allows for modular integration of molecular pathway models, by coupling the in silico model of oxidative stress with the in silico model of C1 metabolism, and 2) derivation of new insights on the effects of oxidative stress on C1 metabolism relative to formaldehyde (HCHO), a toxic molecule, and glutathione (GSH), an important indicator of oxidative homeostasis in living systems. Previous in silico modeling of C1 metabolism, without oxidative stress, observed complete removal of formaldehyde via formaldehyde detoxification pathway and no change in glutathione concentrations. The results from this research of integrative oxidative stress with C1 metabolism, however, demonstrate significant upregulation of formaldehyde concentrations, with concomitant downregulation and depletion of glutathione. Sensitivity analysis indicates that kGSH-HCHO, the rate constant of GSH-HCHO binding, VSHMT, the rate of formation of sarcosine from glycine, and , the rate of superoxide formation significantly affect formaldehyde homeostasis in the C1 metabolism. Future research may employ this integrative model to explore which conditions initiate oxidative stress and the resultant upregulation and downregulation of formaldehyde and glutathione.

Antioxidant Effect of Selenium-containing Glutathione S-Transferase in Rat Cardiomyocytes

As one of the most important antioxidant enzymes, glutathione peroxidase（GPX） protects cells and tissues from oxidative damage, and plays an important role in cardiovascular and cerebrovascular injuries induced by oxida- tive stress. The antioxidant effect of selenium-containing glutathione S-transferase（Se-GST）, a mimic of GPX was investigated on rat cardiomyocytes. To explore the protection function of Se-GST in hydrogen peroxide（H202） chal- lenged rat cardiomyocytes, we examined malondialdehyde（MDA）, lactate dehydrogenase（LDH）, superoxide dismu- tase（SOD） and cell apoptosis. The results demonstrate exposure of rat cardiomyocytes to H202 for 6 and 12 h induced the significant increases of MDA, LDH and apoptosis rate of cardiomyocytes, but pretreatment of rat cardiomyocytes with Se-GST at 0.0005 or 0.001 unit/mL prevents oxidative stress induced by H202 with the decreases of cell apopto- sis. All the results hint Se-GST has antioxidant activity for oxidative stress challenged rat cardiomyocvtes.

Synthesis and electrochemical properties of environmental free Lglutathione grafted graphene oxide/ZnO nanocomposite for highly selective piroxicam sensing

A simple and reliable strategy was proposed to engineer the glutathione grafted graphene oxide/ZnO nanocomposite(glutathione-GO/ZnO)as electrode material for the high-performance piroxicam sensor.The prepared glutathione-GO/ZnO nanocomposite was well characterized by X-ray diffraction(XRD),Fourier transform infrared spectrum(FTIR),X-ray photoelectron spectroscopy(XPS),field emission scanning electron microscopy(FE-SEM),cyclic voltammetry(CV),electrochemical impedance spectroscopy(EIS)and differential pulse voltammetry(DPV).The novel nanocomposite modified electrode showed the highest electrocatalytic activity towards piroxicam(oxidation potential is 0.52 V).Under controlled experimental parameters,the proposed sensor exhibited good linear responses to piroxicam concentrations ranging from 0.1 to 500 μM.The detection limit and sensitivity were calculated as 1.8 μM and 0.2 μA/μM·cm^(2),respectively.Moreover,it offered excellent selectivity,reproducibility,and long-term stability and can effectively ignore the interfering candidates commonly existing in the pharmaceutical tablets and human fluids even at a higher concentration.Finally,the reported sensor was successfully employed to the direct determination of piroxicam in practical samples.

Protective Effect of Reduced Glutathione C_(60) Derivative against Hydrogen Peroxide-induced Apoptosis in HEK 293T Cells

Hydrogen peroxide（H_2O_2） and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene（C_（60）） is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione（GSH） is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative（C_（60）-GSH） was successfully synthesized, and its beneficial roles in protecting against H_2O_2-induced oxidative stress and apoptosis in cultured HEK 293 T cells were investigated. Fourier Transform infrared spectroscopy and 1H nuclear magnetic resonance were used to confirm the chemical structure of C_（60）-GSH. Our results demonstrated that C_（60）-GSH prevented the reactive oxygen species（ROS）-mediated cell damage. Additionally, C_（60）-GSH pretreatment significantly attenuated H_2O_2-induced superoxide dismutase（SOD） consumption and malondialdehyde（MDA） elevation. Furthermore, C_（60）-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H_2O_2 stimulation in HEK 293 T cells. Importantly, these protective effects of C_（60）-GSH were superior to those of GSH. In conclusion, these results suggested that C_（60）-GSH has potential to protect against H_2O_2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.

Effect of extracts from Stachys sieboldii Miq. on cellular reactive oxygen species and glutathione production and genomic DNA oxidation

Objective: To evaluate the antioxidant activity of extracts and fractions from Stachys sieboldii Miq., and to examine its effect on the cellular reactive oxygen species(ROS) and glutathione(GSH) production and genomic DNA oxidation in HT-1080 cells. Methods: The ROS generation induced by H2 O2 was measured by the dichlorofluorescein-diacetate assay. GSH levels were measured using a fluorescent method with mBBr. Genomic DNA oxidative damage was measured with levels of oxidative DNA induced by the reaction of ferritin with H2 O2. Results: The n-hexane, 85% aqueous methanol and n-butanol fractions(0.05 mg/mL concentrations) inhibited H2 O2-induced ROS generation by 63%, 35% and 45%, respectively. GSH levels were significantly increased in both acetone+methylene chloride and methanol extracts(P<0.05). Supplementation of cells with n-hexane significantly increased GSH levels at concentrations of 0.05 mg/mL(P<0.05). Both the acetone+methylene chloride and methanol extracts, as well as all fractions significantly inhibited oxidative DNA damage(P<0.05). Conclusions: These results indicate that cellular oxidation was inhibited by the n-hexane fraction and this fraction may contain valuable active compounds.

Study of Oxidation of Glutathione Treated with Hypochlorous Acid by Capillary Electrophoresis

Capillary electrophoresis (CE) method was developed for the separation and quantification of reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione sulphonic acid (GSO(3)H). Baseline separation was obtained within five minutes. The effects of reaction time and molar ratio of hypochlorous acid (HOCl) to GSH on the oxidation of GSH were investigated.

Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

BACKGROUND： Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione, known as one of the compounds of antioxidant defense, has been shown to inhibit convulsions. Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE： To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN, TIME, AND SETTING： A randomized, controlled, animal experiment. The study was performed at the Department of Physiology, Gaziantep University and Department of Chemistry-Biochemistry,Kahramamaras Sutcu Imam University in 2006. MATERIALS： Pentylenetetrazole and glutathione were purchased from Sigma, USA. METHODS： A total of 80 mice were assigned to 8 groups （n = 10）： normal control, saline control （1 mL normal saline）, convulsive pentylenetetrazole （single intraperitoneal administration of pentylenetetrazole, 60 mg/kg）, convulsive pentylenetrazole plus glutathione （single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione）, five-dose glutathione （intraperitoneal injection of 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days）, single-dose glutathione （single administration of 200 mg/kg glutathione）, pentylenetetrazole kindling （intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1,3, 5, 7, and 10 days）, and pentylenetetrazole kindling plus glutathione group （intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days）. MAIN OUTCOME MEASURES： All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. RESULTS： There were no significant differences in nitric oxide levels between the normal control, saline control, five-dose glutathione, and single-dose glutathione groups （P 〉 0.05）. Nitric oxide levels in the cerebral hemisphere and cerebellum were significantly less in the convulsive pentylenetetrazole group, compared with the convulsive pentylenetetrazole plus glutathione group （P 〈 0.01）, and levels in the pentylenetetrazole kindling group were remarkably greater than the remaining groups （P 〈 0.01 ）. Brain nitric oxide levels in all groups gradually decreased from the right brain stem to the left brain stem, cerebellum, left cerebral hemisphere, and right cerebral hemisphere. CONCLUSION： Glutathione regulated nitric oxide levels in various brain regions of pentylenetetrazole-induced kindling models, and did not affect nitric oxide levels in the control mice. These results indicated that glutathione played a role when nitric oxide was over-produced. In addition, the brain stem exhibited the highest levels of nitric oxide in both control mice and pentylenetetrazole-induced kindling models.

Oxidative stress regulated heme-oxygenase-1 and glutathione S-transferase-m1 gene expression changes in cell lines exposed to melanins

To investigate the effects of oxidative stress on substantia nigra neuronal degeneration and death in patients with Parkinson＇s disease, we treated neuroblastoma cells （SK-N-SH） and glioma cells with Fenton＇s reagent, iron chelating agent, neuromelanin and dopamine melanin. We investigated the changes in expression of nine oxidative stress-related genes and proteins. The levels of mRNAs for heme-oxygenase-1 and glutathione S-transferase-ml were significantly reduced in SK-N-SH cells exposed to oxidative stress, and increased in glial cells treated with deferoxamine. These results revealed that SK-N-SH neurons react sensitively to oxidative stress, which implies different outcomes between these two types of cells in the substantia nigra. Moreover, the influences of neuromelanin and dopamine melanin on cell function are varied, and dopamine melanin is not a good model for neuromelanin.

Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide,glutathione peroxidase,and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO and MPO （P 〈 0.01）. The serum level of GSH-Px was significantly upregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）, compared with the physiological saline group （P 〈 0.05-0.01）. Following medical treatment, serum levels of NO and MPO were significantly downregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）. Serum levels of GSH-Px, NO, and MPO in the LMWH-SOD group were close to those in the sham-operated group （P 〉 0.05）. CONCLUSION： In cerebral ischemia/reperfusion injury, LMWH-SOD conjugate exhibits stronger neuroprotective effects on free radical scavenging, inflammation inhibition, and cytotoxicity inhibition than simple or combined application of LMWH and SOD by downregulating NO and MPO levels and upregulating the GSH-Px level.

Hemin Protects U937 Cells from Oxidative Stress via Glutathione Synthesis

Although heme oxygenase-1 and glutathione play important roles in the antioxidant defense system, the sharing and/or cross-talking of the HO-1 and GSH system remain poorly understood. The object of this study is to determine whether the glutathione system is involved in the antioxidant function of hemin. Hydrogen peroxide decreased the viability of the human leukemic monocyte lymphoma cell line U937. When these cells were pretreated with hemin before the addition of hydrogen peroxide, cell death was prevented. An inhibitor of heme oxygenase-1 or glutathione biosynthesis significantly abolished this protective effect of hemin. These results suggest that both heme oxygenase-1 and glutathione are involved in the protective effects of hemin against U937 cell death, which was induced by hydrogen peroxide. Hemin induced an increase in glutathione levels following the upregulation of the gene expression and protein levels of glutamate-cysteine ligase catalytic subunit. The inhibitor of heme oxigenase-1 inhibited the upregulation of glutamate-cysteine ligase catalytic subunit expression. These results suggest that hemin induces glutathione synthesis through heme oxygenase-1 activation to protect cells from hydrogen peroxide-induced oxidative stress.

Flavonoids Reduce Lipid Peroxides and Increase Glutathione Levels in Pooled Human Liver Microsomes (HLMs)

The effects of each of the flavonoids;genistein (G), quercetin (Q) and kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.

Effect of adjuvant reduced glutathione therapy on vasoactive molecules and oxidative stress in patients with cirrhosis-induced upper gastrointestinal hemorrhage

Objective: To study the effect of adjuvant reduced glutathione therapy on vasoactive molecules and oxidative stress in patients with cirrhosis-induced upper gastrointestinal hemorrhage. Methods: Patients diagnosed with cirrhosis-induced upper gastrointestinal hemorrhage in No. 215 Hospital of Shaanxi Nuclear Industry between June 2015 and March 2017 were selected as the research subjects, and random number table was used to divide them into the GSH group who accepted reduced glutathione combined with conventional therapy and the control group who accepted conventional therapy. Serum levels of liver function indexes, vasoactive molecules and oxidative stress reaction molecules in two groups of patients were detected before treatment and 3 d after treatment. Results: 3 d after treatment, serum ALT, AST, γ-GT, TBIL, PRA, AT-Ⅱ, ALD, MDA, ox-LDL, AOPP and 8-OHdG levels of both groups of patients were significantly lower than those before treatment while SOD, GSH-Px and CAT levels were significantly high than those before treatment, and serum ALT, AST, γ-GT, TBIL, PRA, AT-II, ALD, MDA, ox-LDL, AOPP and 8-OHdG levels of GSH group were significantly lower than those of control group while SOD, GSH-Px and CAT levels were significantly higher than those of control group. Conclusion: The adjuvant reduced glutathione therapy for cirrhosis-induced upper gastrointestinal hemorrhage can improve the liver function, regulate the secretion of vasoactive molecules and reduce the oxidative stress response.

Changes of the glutathione redox system during the weaning transition in piglets, in relation to small intestinal morphology and barrier function

Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione(GSH)redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight(LBW) and normal birth weight(NBW) littermates were assigned to one of three weaning treatments;i.e. weaning at 3 weeks of age(3 w), weaning at 4 weeks of age(4 w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age(3 d3 w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets.Results: Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status(GSH/GSSG Eh) was only observed in the small intestinal mucosa of 3 d3 w weaned piglets at d 5 postweaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran(FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment.Conclusion: Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3 w and 4 w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3 d3 w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function.

Effect of Nicotine on Dopamine and Glutathione Levels in Presence of Oligoelements in Brain Regions of Young Rats——Effect of Nicotine on Brain Regions of Rat

Aim: The purpose of this study was to understand the mechanism of nicotine mediated addiction and the role of oligoelements in reducing its effect. Methods: Male Wistar rats (weight 80 g) were treated with single and repeated doses of nicotine and/or oligoelements as follows: group 1 (control) NaCl 0.9%;group 2, nicotine (1 mg/kg);group 3, oligoelements (50 μl/rat);and group 4, nicotine (1 mg/kg) + oligoelements (50 μl/rat). All drugs were intraperitoneally administered for 4 days. Blood for the measurement of glucose was obtained from all the animals. Samples of the brain regions (cortex, hemispheres and cerebellum + medulla oblongata) of each rat were obtained and used to measure the concentrations of dopamine, GSH levels, and lipid peroxidation (TBARS) using fluorescence and spectrophotometric methods. Results: Glucose level increased in rats treated with nicotine and oligoelements (p < 0.05), while GSH level decreased in cerebellum/medulla oblongata and hemispheres (p < 0.05) of the same animals. TBARS levels increased in cerebellum/medulla oblongata and hemispheres of animals treated with nicotine and oligoelements, but decreased in the same regions (p < 0.05) in rats treated only with oligoelements. The levels of dopamine decreased in cortex and hemispheres, but increased in cerebellum/medulla and oblongata regions of rats treated with both compounds (p < 0.05). Conclusions: Nicotine and oligoelements are associated with increase in the level of glucose, an effect that was more pronounced in the group treated with both drugs. Reduction of oxidative stress and dopamine metabolism may be involved in this effect.