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.ME...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.展开更多
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 ac...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.展开更多
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 glutath...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.展开更多
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 fo...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.展开更多
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 wit...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.展开更多
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 cor...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.展开更多
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 (...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展开更多
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 ...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.展开更多
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 pat...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.展开更多
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...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.展开更多
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...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.展开更多
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 wit...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.展开更多
Glutathione transferases(GSTs) play an important role in the detoxification of xenobiotic/endobiotic toxic compounds. The α-, π-, and/l-classes of cytosolic GSTs have been studied extensively, while Gtt2 from Sacc...Glutathione transferases(GSTs) play an important role in the detoxification of xenobiotic/endobiotic toxic compounds. The α-, π-, and/l-classes of cytosolic GSTs have been studied extensively, while Gtt2 from Saccharo- myces cerevisiae, a novel atypical GST, is still poorly understood. In the present study, we investigated the gluta- thione(GSH) activation mechanism of Gtt2 using the density functional theory(DFT) with the hybrid functional B3LYP. The computational results show that a water molecule could assist a proton transfer between the GSH thiol and the N atom of His133. The energy barrier of proton transfer is 46.0 kJ/mol. The GSH activation mechanism and the characteristics of active site are different from those of classic cytosolic GSTs.展开更多
<span style="font-family:Verdana;">The effects of each of the flavonoids;genistein (G), quercetin (Q) and</span><span style="font-family:""><span style="font-family:V...<span style="font-family:Verdana;">The effects of each of the flavonoids;genistein (G), quercetin (Q) and</span><span style="font-family:""><span style="font-family:Verdana;"> 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. </span><span style="font-family:Verdana;">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</span><span style="font-family:Verdana;"> 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.</span></span>展开更多
[Objective] The aim of this study was to screen Saccharomyces for glutathione over-production. [Method] Ethionine-resistant mutants were obtained through UV mutagenesis and rational screening. [Result] A high GSH-prod...[Objective] The aim of this study was to screen Saccharomyces for glutathione over-production. [Method] Ethionine-resistant mutants were obtained through UV mutagenesis and rational screening. [Result] A high GSH-producing strain HSJB1 was isolated from soil, and the biomass for this strain by flask shaking fermentation was 3.87 g/L while the GSH yield was 91.87 mg/L. According to the morphological, physiological and biochemical characteristics of cells, this strain was primarily identified as Saccharomyces cerevisiae. An ethionine-resistant mutant YBS77 was obtained through UV mutagenesis of the original strain HSJB1, and the biomass for this strain by flask shaking fermentation was 7.60 g dry cell weight/L while the GSH yield was 211.96 mg/L. [Conclusion] The biomass of the mutant obtained by breeding is increased by 96.38% than that of the original strain, and the GSH yield of the mutant obtained by breeding is increased by 130.72% than that from the original strain, which indicates that the breeding method is feasible.展开更多
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 glutathi...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.展开更多
To evaluate the effects of high fat food consisted of tallow (19% of total diets) and cholesterol (2%) on modification of erythrocyte phospholipids, fatty acids composition and glutathione redox- system of male Wistar...To evaluate the effects of high fat food consisted of tallow (19% of total diets) and cholesterol (2%) on modification of erythrocyte phospholipids, fatty acids composition and glutathione redox- system of male Wistar rats with alimentary dysli- pidemia. The results demonstrated that after 30 and 180 days of high-fat feed erythrocyte phos- phatidylinositol and phosphatidylcholine levels were reduced, phosphatidylserine were in-creased. Only on the 90 days of the experiment phosphatidylinositol level increased. In all grow- ups the erythrocyte 18:0 saturated fatty acids and 20:4n6, 22:4n6 polyunsaturated fatty acids (PUFA) were increased. Deficit of n3 PUFA- 20:5n3 and 22:6n3 after 90 and 180 days high fat feed promoted compensatory synthesis from 18:1n9 on 20:3n9. Erythrocyte maleic dialde-hyde increased, glutathione level decreased in all groups of rats after fed with high-fat feed. Glutathione reductase and glutathione peroxi-dase activity decreased in erythrocytes after 30 and 180 days of high-fat feed. In conclusion: high-fat diet during 30-90 days started adaptive answer in lipids of membrane and glutathione redox-system. Important mechanism of adapta-tion of a cellular membrane to high-fat diet is increase major, structuring a membrane phos-phatidylethanolamine and minor, most meta-bolic significant fractions phospholipids (phos- phatidylinositol), keeps homeostasis of 18:2n6 and 22:6n3, 20:3n9 compensatory synthesis, decrease in activity of processes lipid peroxi-dation, activation of enzymes of redox-system glutathione. But prolonging the high-fat feeding (180 days and more) formed failure compensa-tory processes (dysadaptation). It is a risk factor of developmening atherosclerosis, diabetes, steatogepatitis and other diseases.展开更多
基金Priority Academic Program Development of Jiangsu Higher Education Institutions(2022JSPAPD006)。
文摘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.
基金funded by the National Natural Science Foundation of China (Grant Nos.31972394 and 31501748)。
文摘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.
文摘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.
基金supported by the Nature Science Foundation Committee Projects of China(No.30470425)
文摘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.
基金Jiangsu Ordinary University Science Research Project, No. 06XIB320097
文摘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.
文摘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.
文摘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
文摘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.
文摘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.
文摘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.
文摘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.
基金Project of Shaanxi Provincial Natural Science Foundation No:2017JM8163.
文摘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.
基金Supported by the National Natural Science Foundation of China(No.20903045)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20070183046)the Specialized Fund for the Basic Research of Jilin University,China(No.200810018)
文摘Glutathione transferases(GSTs) play an important role in the detoxification of xenobiotic/endobiotic toxic compounds. The α-, π-, and/l-classes of cytosolic GSTs have been studied extensively, while Gtt2 from Saccharo- myces cerevisiae, a novel atypical GST, is still poorly understood. In the present study, we investigated the gluta- thione(GSH) activation mechanism of Gtt2 using the density functional theory(DFT) with the hybrid functional B3LYP. The computational results show that a water molecule could assist a proton transfer between the GSH thiol and the N atom of His133. The energy barrier of proton transfer is 46.0 kJ/mol. The GSH activation mechanism and the characteristics of active site are different from those of classic cytosolic GSTs.
文摘<span style="font-family:Verdana;">The effects of each of the flavonoids;genistein (G), quercetin (Q) and</span><span style="font-family:""><span style="font-family:Verdana;"> 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. </span><span style="font-family:Verdana;">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</span><span style="font-family:Verdana;"> 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.</span></span>
基金Supported by Scientific Research Project of Liaoning Educational Department(20060154)Initial Funds for Doctors in Dalian Nationalities University(20066206)~~
文摘[Objective] The aim of this study was to screen Saccharomyces for glutathione over-production. [Method] Ethionine-resistant mutants were obtained through UV mutagenesis and rational screening. [Result] A high GSH-producing strain HSJB1 was isolated from soil, and the biomass for this strain by flask shaking fermentation was 3.87 g/L while the GSH yield was 91.87 mg/L. According to the morphological, physiological and biochemical characteristics of cells, this strain was primarily identified as Saccharomyces cerevisiae. An ethionine-resistant mutant YBS77 was obtained through UV mutagenesis of the original strain HSJB1, and the biomass for this strain by flask shaking fermentation was 7.60 g dry cell weight/L while the GSH yield was 211.96 mg/L. [Conclusion] The biomass of the mutant obtained by breeding is increased by 96.38% than that of the original strain, and the GSH yield of the mutant obtained by breeding is increased by 130.72% than that from the original strain, which indicates that the breeding method is feasible.
基金supported by SERB(Science and Engineering Research Board),New Delhi,India[File.No:EMR/2014/000020].
文摘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.
文摘To evaluate the effects of high fat food consisted of tallow (19% of total diets) and cholesterol (2%) on modification of erythrocyte phospholipids, fatty acids composition and glutathione redox- system of male Wistar rats with alimentary dysli- pidemia. The results demonstrated that after 30 and 180 days of high-fat feed erythrocyte phos- phatidylinositol and phosphatidylcholine levels were reduced, phosphatidylserine were in-creased. Only on the 90 days of the experiment phosphatidylinositol level increased. In all grow- ups the erythrocyte 18:0 saturated fatty acids and 20:4n6, 22:4n6 polyunsaturated fatty acids (PUFA) were increased. Deficit of n3 PUFA- 20:5n3 and 22:6n3 after 90 and 180 days high fat feed promoted compensatory synthesis from 18:1n9 on 20:3n9. Erythrocyte maleic dialde-hyde increased, glutathione level decreased in all groups of rats after fed with high-fat feed. Glutathione reductase and glutathione peroxi-dase activity decreased in erythrocytes after 30 and 180 days of high-fat feed. In conclusion: high-fat diet during 30-90 days started adaptive answer in lipids of membrane and glutathione redox-system. Important mechanism of adapta-tion of a cellular membrane to high-fat diet is increase major, structuring a membrane phos-phatidylethanolamine and minor, most meta-bolic significant fractions phospholipids (phos- phatidylinositol), keeps homeostasis of 18:2n6 and 22:6n3, 20:3n9 compensatory synthesis, decrease in activity of processes lipid peroxi-dation, activation of enzymes of redox-system glutathione. But prolonging the high-fat feeding (180 days and more) formed failure compensa-tory processes (dysadaptation). It is a risk factor of developmening atherosclerosis, diabetes, steatogepatitis and other diseases.