N-acetylcysteine and reduced glutathione reverse flupirtine-induced liver injury and pro⁃duce other beneficial effects in combination with flupirtine

OBJECTIVE To assess whether N-acetylcysteine(NAC)and reduced glutathione(GSH)are effective in reversing flupirtine-induced hepatotoxicity and whether they have other beneficial effects when combined with flupirtine.METHODS The analgesic effects of NAC and flupirtine were first evaluated in carrageenaninduced inflammatory pain and paclitaxel-induced neuropathic pain.The combination subthreshold⁃ing approach was then used to determine whether the combination of NAC and flupirtine produced synergistic analgesic effects.Hepatotoxicity markers and histopathological examination of the liver were used to assess the efficacy of NAC and GSH in reversing flupirtine-induced hepato⁃toxicity.Finally,the effect of GSH on the safe range of flupirtine was assessed in an acute tox⁃icity assay.RESULTS Flupirtine and NAC pro⁃duced dose-dependent antiallodynic effects evoked by carrageenan and paclitaxel in mice.In the above model,the combination of NAC and flupirtine produced an unexpected synergistic analgesic effect.There were no significant differ⁃ences observed in the hepatotoxicity markers and liver histopathology between the experimen⁃tal group and the control group under NAC and GSH treatment.Finally,GSH(200 mg·kg^(-1))expanded the therapeutic index of flupirtine by 1.77 times.CONCLUSION NAC and GSH are effective in preventing liver damage caused by long-term flupirtine use,which provides a solu⁃tion for the safe and effective treatment of chronic pain with flupirtine.In addition,the other benefi⁃cial effects of NAC and GSH when combined with flupirtine may provide the basis for the devel⁃opment of a new therapy with minimal sideeffects and good efficacy.

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.

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 reduced glutathione assisted therapy on immune function, antioxidant function and inflammatory factor in ovarian cancer after chemotherapy

Objective:To investigate the effect of reduced glutathione adjuvant treatment on immune function, antioxidant function and inflammatory cytokines in ovarian cancer patients after chemotherapy.Result:A total of 100 patients with ovarian cancer who were admitted in our hospital from January 2015 to June 2017. According to the enrollment serial number, divided them into research group and control group each 50 cases, the control group was given conventional chemical drug treatment, the research group were given reduced glutathione adjuvant therapy on the basis of chemical therapy. The T lymphocyte subsets, antioxidant indexes MDA, SOD, T-AOC and inflammatory cytokines TNF-α, IL-6, IL-8 levels change in two groups before chemotherapy (T0), 1 month after chemotherapy (T1) and 3 months (T2) were observed.Result: (1) The CD3+,CD4+,CD4+/CD8+ levels at T1 was decreased than T0, and T2 was significantly increased when compared with T1, The CD8+ level at T1 was higher than T0, and the T2 was significantly decreased than T1 in both groups. The levels of the CD3+, CD4+, CD4+/CD8 at T1, T2 in the research group were higher than the control group, while the levels of CD8+ in the research group was lower than the control group. The difference was statistically significant. (2) The level of MDA at T1 was higher than T0, T2 was significantly lower than T1 in both groups. The levels of SOD and T-AOC at T1 were decreased than T0, and T2 was significantly higher than T1. The levels of SOD and T-AOC at T1, T2 in the research group were higher than in the control group, while the MDA level was lower than in the control group. The difference was statistically significant. (3) The levels of TNF-α, IL-6 and IL-8 at T1 in two groups were significantly higher than T0, and the T2 decreased significantly when compared with T1, The levels of TNF-α, IL-6 and IL-8 at T1, T2 in the research group were lower than in the control group. The difference was statistically significant.Conclusion: The reduced glutathione adjuvant chemotherapy for postoperative ovarian cancer can help to protect the body's immune function, antioxidant function and reduce inflammation factor.

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.

Effect of the reduced glutathione antioxidation combined with conventional antiviral drugs on hepatic fibrosis in patient with hepatitis b cirrhosis

Objective: To study the effect of the reduced glutathione antioxidation combined with conventional antiviral drugs on hepatic fibrosis in patient with liver cirrhosis. Methods: A total of 300 patients with hepatitis b cirrhosis who were treated in Shangluo Central Hospital between August 2012 and August 2016 were collected and divided into the control group (n=159) who received conventional antiviral therapy and the observation group (n=141) who received reduced glutathione antioxidation combined with conventional antiviral drug therapy. The differences in serum levels of fibrosis indicators, inflammatory factors and oxidative stress indexes were compared between the two groups of patients before and after treatment. Results: Before treatment, differences in serum levels of fibrosis indexes, inflammatory factors and oxidative stress indexes were not statistically significant between two groups of patients. After treatment, serum HA, Ⅳ-C, LN, PCⅢ, PCT, IL-6, IL-22, IL-31, TNF-α and MDA levels of both groups of patients were lower than those before treatment while GSH-Px and T-SOD levels were higher than those before treatment, and serum HA, Ⅳ-C, LN, PCⅢ, PCT, IL-6, IL-22, IL-31, TNF-α and MDA levels of observation group after treatment were lower than those of control group while GSH-Px and T-SOD levels were higher than those of control group. Conclusion: Reduced glutathione antioxidation combined with conventional antiviral drugs can effectively inhibit the fibrosis process in patients with hepatitis b cirrhosis, which is because that it reduces the degree of inflammation and oxidative stress reaction.

Effects of Reduced Glutathione to Centrifuged and Non-centrifuged Fresh Chilled Stallion Semen on Progressive Motility of Spermatozoa over 72 h

The aim of the current study was to evaluate the effects of supplementation of an inexpensive stallion semen extender(Next Generation■ Dr.Kenny’s with Amikacin and K-Penn)with 1 mM of the antioxidant reduced glutathione(GSH)on the progressive motility of cooled stallion semen over a period of 72 h.Both centrifuged and non-centrifuged semen samples were evaluated from six Standardbred stallions collected three times each,with one week between collections for each stallion.For centrifuged samples,non-cushioned centrifugation was done at 750 g for 10 min.All semen samples were extended to a final concentration of 50 million total cells per milliliter and stored in Equine Express II stallion semen shipping containers.Non-centrifuged samples without GSH declined from an initial mean progressive motility of 70.3%at 0 h to 9.1%at 72 h.Non-centrifuged samples with added GSH declined from an initial mean progressive motility of 70.3%at 0 h to 7.1%at 72 h.Centrifuged samples without added GSH declined from an initial mean progressive motility of 70.3%at 0 h to 46.1%at 72 h.Centrifuged samples with added GSH declined from an initial mean progressive motility of 70.3%at 0 h to 40.3%at 72 h.The results of this study did not find significant improvement in the progressive motility over time for spermatozoa prepared in a traditional skim-milk based extender with antibiotics as a result of addition of GSH to either centrifuged or non-centrifuged semen.These findings suggest that centrifugation of fresh chilled extended stallion semen may be a good idea for any semen that may be used at time points greater than 24 h after collection.

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.

Reduced glutathione alleviates the toxic effect of 6-hydroxydopamine on bone marrow stromal cells

We studied the effect of reduced glutathione on bone marrow stromal cells （BMSCs） treated with 6-hydroxydopamine （6-OHDA）, which shows a toxic effect on dopaminergic neurons. The proliferation of BMSCs treated with 6-OHDA decreased, while that of BMSCs treated with reduced glutathione increased. The proliferation of BMSCs treated with both 6-OHDA and reduced glutathione was significantly higher compared with that treated with 6-OHDA alone. These findings indicate that reduced glutathione alleviates the toxic effect of 6-OHDA on BMSCs.

The effect of reduced glutathione on the chondrogenesis of human umbilical cord mesenchymal stem cells

It has been discussed whether reduced glutathione (GSH) could promote the chondrogenic differentiation ability of human umbilical cord mesenchymal stem cells (hUC-MSCs). hUC-MSCs were isolated from human umbilical cord and their specificity was identified, then induced into cartilage-like cells in chondrogenic induction medium with transforming growth factor beta 1 (TGF-β1), especially with GSH. The morphological change before and after induction was observed through inverted phase contrast microscope, Type II collagen (COL2-A1) and glycosaminoglycan (GAG) were analyzed qualitatively by Toluidine blue and immunofluorescence technique, respectively, the contents of COL2-A1 and GAG were estimated from the determination of hydroxyproline content and Alcian Blue method separately. The mRNA expressions of GAG and COL2-A1 were assayed by real-time fluorescence quantitative PCR. After continuously cultured for 21 days with GSH, Toluidine blue staining and immunofluorescence reaction were all positive in basic induction medium group (group B), basic induction medium +0.5% dimethylsulfoxide (DMSO) group (group BD) and basic induction medium +0.5% DMSO +500 μM GSH group (group BDG). Moreover, compared with group B and group BD, the contents of COL2-A1 and GAG in group BDG relatively increased and the mRNA expression level of COL2-A1 and GAG also comparatively increased (P < 0.05) and both had a significant statistical significance (P < 0.05). So GSH might promote the induction of hUC-MSCs to differentiate into cartilage-like cells.

Role of Exogenous Reduced Glutathione on Time Dependent ^(203)Hg Distribution in Liver and Kidney of a Freshwater Teleost, Anabas testudineus

Time-dependent tissue distribution of mercury(Hg) was studied in a freshwater perch,Anabas testudineus which revealed that the liver and kidneys are the major sites of Hg reten tion. The role of reduced glutathione (GSH) in the clearance of Hg was also investigated to e valuate the ameliorative effect of this nucleophile. For this purpose, the perch was given GSH 15 min before or after they received 203Hg by injection. The fish were then sacrificed at 24 h and 48 h later. The results clearly indicate that exogenous GSH can significantly reduce Hg retention in both the liver and kidneys, demonstrating a direct role of this nucleophile in the amelioration of Hg-induced toxicity in the early phase of intoxication

Reduced-glutathione concentrations in Boleophthalmus pectinirostris tissues exposed to benzo(a)pyrene

The concentrations of reduced-glutathione ( GSH) in liver and ovary of Boleophthalmus pectinirostris are quantified. The concentrations of GSH in the ovary are much higher than that of GSH in the liver(nearly 3 times of the liver). The study also investigates the changes of GSH contents in the two organs while the fishes were exposed to benzo(a)pyrene(BaP) at concentrations of 0, 0.05, 0.2 and 0.5 mg/L respectively for up to a week. The concentrations of GSH in the liver of BaP-exposed fish increased significantly with dose, whereas the concentrations of GSH in the ovary decreased significantly compared to controls. The results suggested that both the liver and the ovary are the primary organ in BaP metabolism, and that the changes of GSH levels may represent an adaptive response or toxic effect to Bap exposure.

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.

Influence on liver function of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer

Objective:To explore the influence on liver function of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer.Methods:A total of 120 cases of elderly patients with advanced liver cancer from digestive surgery in-patient department of our hospital during the period of January 2014 and January 2016 were selected as the research object, the patients were divided into two groups by using the random number table method,each for 60 cases.The control group were given conventional drugs chemotherapy, the study group were given hepatic artery interventional chemoembolization combined reduced glutathione therapy, serum liver function indexes of Direct Bilirubin(DBil), Total Bilirubin(TBil), Aspartate Transaminase(AST) and Alanineamino Transferase (ALT)were detected by using automatic biochemical analyzer. Results: The clinical remission rate of study group was significantly higher than the control group, the recurrence rate was obviously lower than the control group,compared between the two groups with statistically significant differences. The average survival time of study group (29.36±6.25) months, was significantly longer than the control group (18.02±4.16) months .Before the treatment, serum DBil, TBil, AST and ALT levels compared between the two groups with no statistically significant differences,after the treatment,the indexes of study group was significantly lower than the control group. The indexes levels compared between pre-therapy and post-therapy in study group with no statistically significant differences, while the indexes levels of post-therapy in the control group were significantly higher than those pre-therapy. Before the treatment, the life quality score compared between the two groups with no statistically significant differences, after treatment,the score of all patients were significantly higher than those pre-therapywhich the score of study group was significantly higher than the control group.The incidence rate of drug adverse reactions compared between the two groups with no statistically significant differences.Conclusion: The clinical efficacy of hepatic artery interventional chemoembolization combined reduced glutathione therapy for elderly patients with advanced liver cancer is satisfying, and helps to significantly improve liver function, improve life quality, it is worth popularization and application in the clinical practice.

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.

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.

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.

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.