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.

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.

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.

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.

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.

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.

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.

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.

Theoretical Study on GSH Activation Mechanism of a New Type of Glutathione Transferase Gtt2

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.

生物反馈电刺激疗法对围绝经期女性盆底功能障碍患者血清SOD、GSH-Px水平的影响

目的观察生物反馈电刺激疗法治疗围绝经期盆底功能障碍性疾病(PFD)患者的临床效果及对血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平的影响。方法收集2019年8月至2022年8月在长沙市第三医院妇产科就诊的204例PFD患者作为研究对象,以随机数字表法分成对照组(102例)与试验组(102例)。对照组给予盆底肌肉锻炼(即Kegel运动),试验组同时联合生物反馈电刺激疗法治疗,比较两组患者临床效果,以及治疗前后盆底肌力、生活质量及血清SOD与GSH-Px水平变化。结果治疗后,试验组总有效率(96.08%)高于对照组(82.35%)[(χ2=4.993,P=0.025)];治疗后,试验组盆底肌力、Ⅰ类/Ⅱ类肌纤维最大值均明显优于对照组[(4.31±0.80)级vs(3.09±0.76)级,(31.69±7.62)uv vs(23.19±7.17)uv,(44.07±12.89)uv vs(34.48±13.15)uv(t=-7.896,-5.802,-3.719,P均<0.01)];治疗后,试验组患者血清SOD、GSH-Px水平明显优于对照组[(5501.28±512.37)pg/mL vs(5096.31±526.42)pg/mL,(824.33±139.69)pmol/L vs(542.68±117.54)pmol/L(t=-3.937,-11.018,P均<0.01)];治疗后,试验组患者盆底功能障碍量表(PFDI-20)总分与其分量表评分以及盆底障碍影响简易量表(PFIQ-7)总分与分量表评分下降显著优于对照组(t=1.967~4.840,P均<0.05)。结论生物反馈电刺激疗法有助于围绝经期女性PFD患者增强盆底肌力,提高血清SOD、GSH-Px水平,提升患者生活质量。

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.

双核Pt(Ⅳ)配合物与Guanosine-5′-Monophosphate和Glutathione反应的核磁共振光谱研究(英文)

合成了一个新型的双核Pt(Ⅳ)配合物｛[cis-Pt(NH3)2Cl(OH)2]2(4,4′-methylenedianiline)｝(NO3)2(化合物1)及相应的15N标记化合物｛[cis-Pt(15NH3)2Cl(OH)2]2(4,4′-methylenedianiline)｝(NO3)2(化合物15N-1)。利用1HNMR和ESMS进行了结构表征,化合物15N-1的2D[1H,15N]HSQCNMR发现,该化合物在水溶液中存在同分异构体。2D[1H,15N]HSQCNMR技术跟踪了化合物15N-1与Guanosine-5′-Monophosphate(5′-GMP)和Glutathione(GSH)的反应。结果显示,5′-GMP能在0.5h内将化合物1还原,而GSH在6h以后才能够部分的将化合物1还原。化合物1所表现出来的反应性能将有利于提高其治疗效果和降低毒副作用。

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.

The effect of high fat food on erythrocyte phospholipids, fatty acids composition and glutathione redox-system of rats with alimentary dyslipidemia

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.

Glutathione Production by <i>Yarrowia lipolytica</i>Showing Both Methyglyoxal Resistance and a High Activity of Glutathione Synthetase

Although Yarrowia lipolytica is an important host strain, there have so far been few studies on the production of glutathione by the strain. We therefore performed a study to obtain an improved strain of Y. lipolytica ATCC20688, which could produce a high yield of glutathione. First, the capability of glutathione production in the ATCC20688 strain was estimated. In comparison with other yeasts, the yield of this strain was higher than those in Pichia strains. Furthermore, this strain could produce glutathione by assimilating sodium oleate. We next performed mutation and gene cloning to improve the yield. After the yield of glutathione was improved in the isolated methylglyoxal-resistant mutant (MGR3), the glutathione synthetase gene was cloned into the MGR3 strain. By using this recombinant strain, we could reach the maximum yield and intracellular content of glutathione of 54 mg/L-medium and 30 mg/g-dry cell weight, respectively.