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At least 217 records · Page 12Linked to original sources
PubMed2003

Computational and experimental studies on the distribution of addition and substitution products of the microsomal glutathione transferase 1-catalyzed conjugation of glutathione with fluoroalkenes.

The glutathione transferase-catalyzed reaction of glutathione with haloalkenes results in the formation of addition or substitution products or both. Glutathione conjugates of haloalkenes may be metabolized and excreted at different rates, may follow different metabolic pathways, and may exhibit different toxicities. Microsomal glutathione transferase 1 (MGST1)-catalyzed conjugation of chlorotrifluoroethene, hexafluoropropene, and 2-(fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene results in differing proportions of addition and substitution products. The aim of the present study was to develop a computational model to predict the outcome of the MGST1-catalyzed reaction of glutathione with haloalkenes. An ab initio computational study of the reaction of ethanethiolate, a surrogate for glutathione, with the chlorotrifluoroethene, hexafluoropropene, and 2-(fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene was conducted. An empirical study was also conducted to quantify the distribution of addition and substitution products that resulted from the MGST1-catalyzed reaction of glutathione with these fluoroalkenes. The results show that this computational model accurately predicted the distribution of the addition and substitution products that result from the MGST1-catalyzed reaction of glutathione with these fluoroalkenes.

Alkenes↗
PubMed2000

Preferential resistance of dopaminergic neurons to the toxicity of glutathione depletion is independent of cellular glutathione peroxidase and is mediated by tetrahydrobiopterin.

Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD) and could initiate dopaminergic neuronal degeneration. Nevertheless, experimental glutathione depletion does not result in preferential toxicity to dopaminergic neurons either in vivo or in vitro. Moreover, dopaminergic neurons in culture are preferentially resistant to the toxicity of glutathione depletion, possibly owing to differences in cellular glutathione peroxidase (GPx1) function. However, mesencephalic cultures from GPx1-knockout and wild-type mice were equally susceptible to the toxicity of glutathione depletion, indicating that glutathione also has GPx1-independent functions in neuronal survival. In addition, dopaminergic neurons were more resistant to the toxicity of both glutathione depletion and treatment with peroxides than nondopaminergic neurons regardless of their GPx1 status. To explain this enhanced antioxidant capacity, we hypothesized that tetrahydrobiopterin (BH(4)) may function as an antioxidant in dopaminergic neurons. In agreement, inhibition of BH(4) synthesis increased the susceptibility of dopaminergic neurons to the toxicity of glutathione depletion, whereas increasing BH(4) levels completely protected nondopaminergic neurons against it. Our results suggest that BH(4) functions as a complementary antioxidant to the glutathione/glutathione peroxidase system and that changes in BH(4) levels may contribute to the pathogenesis of PD.

Animals↗
PubMed1996

Peroxynitrite modification of glutathione reductase: modeling studies and kinetic evidence suggest the modification of tyrosines at the glutathione disulfide binding site.

The catalytic properties of glutathione reductase for its substrate, glutathione disulfide, were altered following a 60 s exposure to a 100-fold molar excess of peroxynitrite; the K(M) value was increased by approximately 2.5-fold and the V(max) value was decreased by approximately 1.7-fold. The kinetic alterations are thought to result from nitrotyrosine formation as the intrinsic Tyr fluorescence is diminished. The UV-visible spectrum of glutathione reductase exhibited absorbance at approximately 423 nm, characteristic of nitrotyrosine. In addition, the presence of nitrotyrosine has been detected by Western immunoblots with an anti-nitrotyrosine antibody. The peroxynitrite-induced inactivation is not observed in the presence of excess glutathione disulfide. However, excess NADPH offered no protection against peroxynitrite-induced inactivation. These observations suggest that the modification of approximately 1.8 Tyr per subunit, at or near the glutathione disulfide binding domain, probably results in the observed catalytic alterations. To test this hypothesis, the two tyrosines closest to the glutathione disulfide binding domain (Tyr114 and Tyr106), as indicated by the X-ray crystallographic data [Karplus and Schulz (1989) J. Biol. Chem., 210, 163-180], were each converted to nitrotyrosines by molecular modeling and the structure energy was minimized. These theoretical calculations indicate that the bond lengths between Tyr114-O and the Gly-N and Cys II-N of glutathione disulfide bound to glutathione reductase (Karplus and Schulz, 1989) increased by 3.0 and 4.3 A, respectively, upon nitration. In the case of Tyr106 the 0-Cys II-N distance also increases by approximately 1.6 A. The loss of these hydrogen bonding contacts is likely to result in the observed catalytic alterations upon reaction with peroxynitrite.

Animals↗
PubMed2006

New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix.

Human glutathione transferase A1-1 is a well studied enzyme, but despite a wealth of structural and biochemical data a number of aspects of its catalytic function are still poorly understood. Here, five new crystal structures of this enzyme are described that provide several insights. Firstly, the structure of a complex of the wild-type human enzyme with glutathione was determined for the first time at 2.0 angstroms resolution. This reveals that glutathione binds in the G site in a very similar fashion as the glutathione portion of substrate analogues in other structures and also that glutathione binding alone is sufficient to stabilize the C-terminal helix of the protein. Secondly, we have studied the complex with a decarboxylated glutathione conjugate that is known to dramatically decrease the activity of the enzyme. The T68E mutant of human glutathione transferase A1-1 recovers some of the activity that is lost with the decarboxylated glutathione, but our structures of this mutant show that none of the earlier explanations of this phenomenon are likely to be correct. Thirdly, and serendipitously, the apo structures also reveal the conformation of the crucial C-terminal region that is disordered in all previous apo structures. The C-terminal region can adopt an ordered helix-like structure even in the apo state, but shows a strong tendency to unwind. Different conformations of the C-terminal regions were observed in the apo states of the two monomers, which suggests that cooperativity could play a role in the activity of the enzyme.

Binding Sites↗
PubMed2004

A randomized, double-blind, placebo controlled trial of melatonin add-on therapy in epileptic children on valproate monotherapy: effect on glutathione peroxidase and glutathione reductase enzymes.

AIMS: To compare the effect of add-on melatonin with placebo on the antioxidant enzymes (glutathione peroxidase and glutathione reductase) in epileptic children on valproate monotherapy. METHODS: In a double-blind, randomized, placebo controlled trial, the effect of add-on melatonin administration on the antioxidant enzymes in epileptic children on valproate (VPA) monotherapy was assessed. A total of 31 patients met the entry criteria. 16 patients were randomly allocated to receive add-on melatonin, and 15 to receive add-on placebo. Blood samples (5 ml) were collected just before the morning dose of valproate for baseline values of glutathione peroxidase and glutathione reductase enzymes, and then after 14 days of add-on melatonin/placebo. Blood was then centrifuged at 3500 r.p.m., serum separated and stored in deep freezer at -20 degrees C until assay of glutathione reductase. Heparinized blood was collected and stored at -20 degrees C in eppendorfs in the deep freezer for assay of glutathione peroxidase. All activity assays were performed on the Ames (Technicon) RA 50 chemistry analyser. RESULTS: Fifteen patients in the add-on melatonin group and 14 patients in the add-on placebo group were finally assessed. There was an increase in the activity of antioxidant enzymes, glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rd), in the add-on melatonin (MEL) group as compared with a reduction in the same in the add-on placebo group (P). After the addition of melatonin/placebo in the respective groups, there was a 7.5% decrease in GSH-Px in the valproate + placebo group, whereas a 11.9% increase in the valproate + melatonin group was observed, the difference between the groups being not statistically significant (P = 0.29). On administration of melatonin/placebo, the post-treatment concentrations of GSSG-Rd in the valproate + placebo group decreased from 92.0 U l(-1) to 67.0 U l(-1) and increased from 82.0 U l(-1) to 113.0 U l(-1), in the valproate + melatonin group, respectively, the difference between them being statistically significant (P = 0.05). The percentage change in the values of GSSG-Rd in the two groups was statistically significant (P = 0.005). CONCLUSIONS: Melatonin exerts neuroprotection due to its antioxidant, antiexcitotoxic and free radical scavenging properties within the central nervous system. Melatonin, thus, as an adjunct, can be a putative neuroprotector in conditions involving oxidative stress like epilepsies.

Anticonvulsants↗
PubMed1993

A glutathione S-transferase with glutathione-peroxidase activity from Arabidopsis thaliana. Molecular cloning and functional characterization.

A full-length cDNA clone for a novel glutathione S-transferase was isolated from Arabidopsis thaliana and characterized. The cDNA encodes a polypeptide of 218 amino acids with a calculated molecular mass of 24,363 Da. The sequence was most related to the theta class within the glutathione-S-transferase superfamily of enzymes. The protein encoded by the cDNA was functionally expressed and enzymically active in Escherichia coli; glutathione-S-transferase activity with the standard enzyme substrate 1-chloro-2,4-dinitrobenzene was demonstrated (apparent Km, 10 mM; apparent Km for glutathione, 0.08 mM). The enzyme is substrate specific and did not use several electrophilic reduced-glutathione acceptor molecules for conjugation. However, it efficiently catalyzed the conversion of 13-hydroperoxy-9,11,15-octadecatrienoic acid (Km, 0.67 mM) as well as 13-hydroperoxy-9,11-octadecadienoic acid (Km, 0.79 mM) to the corresponding hydroxy derivatives with concomitant formation of oxidized glutathione. The enzyme did not use H2O2 as substrate. Thus, the cloned A. thaliana enzyme functions as glutathione peroxidase and, in the plant cell, may be involved in the removal of reactive organic hydroperoxides, such as the products of lipid peroxidation. The enzyme is structurally and enzymatically, however, unrelated to the selenium-containing glutathione peroxidases. Enzymic and immunoblotting data suggest that the A. thaliana enzyme is soluble and constitutively expressed in vegetative rosettes, but is under developmental control during the transition to bolting and flowering.

Amino Acid Sequence↗
PubMed2005

Augmentation of cisplatin sensitivity in cisplatin-resistant human bladder cancer cells by modulating glutathione concentrations and glutathione-related enzyme activities.

OBJECTIVES: To investigate the roles of glutathione and glutathione-S-transferase (GST) in cisplatin-resistance mechanisms in human bladder cancer, by using glutathione-depleting or GST-blocking agents. MATERIALS AND METHODS: Cisplatin-resistant human bladder cancer cell lines were established by continuous exposure of T24 cells to increasing concentrations of cisplatin. Buthionine sulphoximine (BSO), ethacrynic acid and indomethacin were used to deplete glutathione or block GST. Intracellular glutathione content, GST activity and cisplatin cytotoxicity were determined after exposing parental and drug-resistant cell lines to these agents. RESULTS: Intracellular glutathione content and GST activity were significantly decreased, and cisplatin cytotoxicity significantly enhanced, in both parental and resistant cell lines by glutathione-depleting or GST-blocking agents. However, the resistance of cisplatin-resistant cell lines did not fully recover to that of the parental cells with combined BSO and indomethacin. CONCLUSIONS: Both increased glutathione content and GST activity are significant in the cisplatin resistance of human bladder tumour cells. Because BSO, ethacrynic acid and indomethacin caused a partial recovery of resistance in the cisplatin-resistant cell line, further studies are needed to investigate their efficacy for treating patients with metastatic bladder carcinoma resistant to cisplatin.

Antineoplastic Agents↗
PubMed1991

Decreased reduced glutathione and glutathione reductase activity in subjects with hemoglobin C.

Erythrocyte catalase, reduced glutathione, glutathione peroxidase and glutathione reductase were determined in 17 normal black controls, 8 subjects with Hb AC, 12 with Hb SC, 1 with Hb CC and 18 patients with sickle cell anemia. Catalase and glutathione peroxidase activities were decreased in sickle cell anemia. Reduced glutathione and glutathione reductase activity were significantly lower in subjects with Hb C (AC, CC, SC). Differences were observed between Hb C, Hb S and Hb A as regards red cell dehydration, intracellular crystallization, enhanced potassium efflux, an increased number of titratable SH groups in Hb C and the binding of Hb C to band 3 on the inner membrane surface. A decrease in reduced glutathione, probably due to inhibition or decreased synthesis of glutathione reductase, was also observed. All these factors may determine oxidation of Hb C, possibly contributing to the hemolysis in patients with Hb C disease.

Adolescent↗
PubMed1983

Lipoperoxide levels, glutathione status and glutathione peroxidase activity in liver and tumors of mice bearing the Lewis lung carcinoma.

Lipoperoxides, glutathione status and glutathione peroxidase activity have been determined in normal and neoplastic tissues of control and tumor-bearing mice, tissues from both groups being assayed 5, 7, 9, 11, 13 and 15 days after inoculation. The ratio of hepatic reduced: oxidized glutathione increased in tumor-bearing animals as the tumor increased in size. This ratio was 2.5-fold higher at 15 days than at 10 days after tumor inoculation. In both tumor and hepatic tissue the alteration in the ratio was the result of both an increase in reduced glutathione and a decrease in oxidized glutathione levels. In tumor tissue the progressively increasing reduced glutathione content correlated closely with tumor growth. The presence of a tumor did not significantly affect hepatic glutathione peroxidase activity and there was no significant difference between tumor enzyme activity assayed at 2-day intervals between 9 and 15 days after inoculation. The livers of tumor-bearing animals had significantly higher lipoperoxides than control mice, the levels increasing progressively with tumor growth. Tumor lipoperoxides were also high, usually in excess of the hepatic level. The lungs of nontumored littermates, which were compared with the carcinoma as reference tissue, showed no significant change in either glutathione peroxidase activity or lipoperoxide levels when monitored over the same period.

Animals↗
PubMed1983

[Changes in the oxidation-reduction system of glutathione--glutathione reductase [NAD(P). H] in the blood and tissues of white rats exposed to high and low temperatures].

The content of different forms of glutathione and the NADPH-dependent glutathione reductasa activity in blood, brain, liver and sceletal muscle of the white rats exposed to low and high temperatures have been investigated. It was shown that in general cooling of animals the amount of glutathione in blood, brain and liver increases, the glutathione reductasa [NAD(P)H] activity decreases. Under super-heating conditions concentration of all forms of glutathione in blood and tissues and the glutathione reductasa activity reduce. Data obtained permitted to assume the considerable role of the changes of the glutathione-glutathione reductasa system state in the realization of temperature factors action.

Animals↗
PubMed1988

Glutathione and glutathione metabolizing enzymes in yeasts.

Total glutathione content, glutathione peroxidase, glutathione transferase and glutathione reductase activities have been measured in 12 species of yeasts. All the strains tested contained glutathione, though in different amounts, as well as the above mentioned enzymes. To discriminate between the selenium-dependent and the selenium-independent form, glutathione peroxidase activity has been measured with both H2O2 and cumene hydroperoxide. Rhodotorula glutinis appeared to be the only strain in which the selenium-dependent form was not found, but this yeast exhibited the highest level of selenium-independent glutathione peroxide activity as compared to the other strains.

Glutathione↗
PubMed1992

Effect of L-penicillamine hydantoin, an analogue of glutathione, on rat liver glutathione peroxidase, reductase and transferase reactions.

In soluble fractions prepared from rat liver homogenates, L-penicillamine hydantoin appeared to be, on the basis of SH consumption measurements, a substrate for glutathione peroxidase but not transferase reactions. When glutathione is incubated with rat liver soluble proteins in the presence of penicillamine hydantoin, formation of oxidized glutathione is inhibited. Calculations from Lineweaver-Burk plots point out that inhibition by L-penicillamine hydantoin of the peroxide-dependent oxidations of glutathione is mixed, since both apparent Km and Vmax values are modified. Preincubation of rat liver soluble proteins with L-penicillamine hydantoin led to a progressive inactivation of glutathione peroxidase. The kinetics of this inactivation process with respect to time and inactivator concentration were studied. Inclusion in the preincubation mixture of SH-containing molecules such as dithiothreitol, L-cysteine or glutathione protected the enzyme against inactivation. However, none of these molecules and neither hydantoin, Triton X-100, phenol, nor dialysis could reverse the enzyme from inactivated to activated form. Mitochondrial glutathione peroxidase was inhibited and inactivated by L-penicillamine hydantoin to the same extent as its cytosolic counterpart. Modifications by penicillamine hydantoin of various subcellular markers enzymes (lactate dehydrogenase, N-acetyl beta-glucosaminidase, arylsulfatase C, butyryl-CoA dehydrogenase, lauryl-CoA and glycolate oxidases) were of weak amplitude consisting of either inhibition, inactivation or stimulation.

Animals↗
PubMed2000

Effect of lead concentration on the level of glutathione, glutathione S-transferase, reductase and peroxidase in human blood.

Incubation of human whole blood for 24 h at 37 degrees C in the presence of 100-400 microg/dl lead chloride or lead acetate caused a concentration-dependent decrease in the level of reduced glutathione up to 40%. Similarly, the activities of glutathione reductase, glutathione peroxidase and glutathione S-transferase were decreased up to 25%, 50%, and 19%, respectively. Moreover, 100 microg/dl lead chloride or lead acetate slowed the process of glutathione regeneration, and delayed the time for complete regeneration from 20 to 40 min. When glutathione S-transferase was purified by affinity chromatography on Sepharose-linked glutathione, incubated with lead chloride or lead acetate, a concentration-dependent inhibition of the enzymatic activity was observed reaching 50% inhibition at a lead salt concentration of 6000 microg/dl.

Chromatography, Affinity↗
PubMed1988

Glutathione and glutathione-dependent enzymes in ovarian adenocarcinoma cell lines derived from a patient before and after the onset of drug resistance: intrinsic differences and cell cycle effects.

The regulation of glutathione and various glutathione-dependent enzymes has been studied in two ovarian adenocarcinoma cell lines derived from a patient before (PE01) and after (PE04) the onset of drug resistance to cis-platinum, chlorambucil and 5-fluorouracil. Reduced glutathione levels were higher in the drug resistant cells (PE04). This could possibly be attributed to a much higher (6.5-fold) gamma-glutamyl-transpeptidase activity. In addition, glutathione-S-transferase (GST) and glutathione peroxidase were 2.9- and 2.3-fold higher in this cell line. Analysis of the GST subunit composition showed both cell lines contained high levels of the acidic GST and lower concentrations of a basic isozyme. The difference in GST activity between PE01 and PE04 did not appear to be related to the levels of these GST subunits. GSH, glutathione peroxidase and gamma-glutamylcysteinyl synthetase were all found to be regulated during the cell cycle, higher levels being detected in logarithmic versus confluent cultures of PE01 and PE04 and MCF7. This did affect some of the differences between PE01 and PE04 and therefore may be a contributing factor to the differential sensitivity of these cells to cytotoxic compounds. The above data provide the first evidence that tumour cells obtained from a patient before and after the onset of drug resistance have significant differences in glutathione-dependent enzyme content.

Adenocarcinoma↗
PubMedDate not supplied

[The effect of emotional-painful stress, hypoxia, and adaptation to it on the activity of enzymes for metabolizing glutathione and concentration of glutathione in rat organs].

The stress activates glutathione peroxidase in the heart, liver, and kidney, glutathione transferase in the heart and liver, inhibits gamma-glutamyl transferase in the liver; the activity of glutathione reductase and the content of reduced glutathione were unchanged. Two-four-minute hypercapnic hypoxia unchanged the activity of glutathione metabolic enzymes. The activity of the above enzymes decreases in some organs at the death caused by 2-15-minute hypoxia. Long-term intermittent adaptation to hypobaric hypoxia lowers the activity of glutathione peroxidase, -transferase and -reductase. The biological value of the two types of enzymatic responses may be different: stress-induced activation of glutathione metabolic enzymes can enhance resistance to stress and xenobiotics; however, their inhibition during hypoxic adaptation may produce the opposite effect.

Adaptation, Physiological↗
PubMed1996

Response of endogenous reduced glutathione through hepatic glutathione redox cycle to enhancement of hepatic lipid peroxidation with the development of acute liver injury in mice intoxicated with carbon tetrachloride.

In the liver of male ddY mice intoxicated once with carbon tetrachloride (CCl4), the change in lipid peroxide (LPO) level with the development of damage over a 24 hr period after i.p. treatment of the toxicant (1.0 mL/kg) was compared with the changes in reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, GSSG/GSH ratio, and activities of the glutathione redox cycle-related enzymes such as Se-dependent glutathione peroxidase (Se-GSH-px), glutathione reductase (GSSG reductase), and glucose-6-phosphate dehydrogenase (G-6-PDH) and of Se-independent glutathione peroxidase (non-Se-GSH-px) with the development of damage during the same period. An apparent liver injury was observed 0.5 hr after CCl4 treatment and the injury progressed rapidly later than 8 hr, judging from the activities of serum transaminases, marker enzymes of liver cell damage. Hepatic LPO level slightly increased once during the first 4 hr after CCl4 treatment and a marked increase in the level occurred later than 12 h, while serum LPO level increased later than 12 h. Hepatic GSH level decreased rapidly during the first 4 hr after CCl4 treatment and the decreased level recovered slowly thereafter, although the recovered level did not reach the control level. Hepatic GSSG level rapidly increased once during the first 1 hr after CCl4 treatment and an increase in the level occurred again later than 12 h. Hepatic GSSG/GSH increased during the first 1 hr and later than 8 hr after CCl4 treatment, although the ratio was maintained above the control level later than 0.5 h. Hepatic Se-GSH-px activity increased during the first 2 hr after CCl4 treatment and later than 8 h, while hepatic non-Se-GSH-px activity increased during the first 1 hr but decreased below the control level at 8 and 12 h. Hepatic GSSG reductase activity decreased during the first 2 hr after CCl4 treatment but the decrease activity returned up to the control level at 8 h. Hepatic G-6-PDH activity increased rapidly during the first 2 hr after CCl4 treatment and the increase proceeded slowly thereafter. These results indicate that although hepatic lipid peroxidation is enhanced at early and progressed stages of liver injury in mice intoxicated once with CCl4, endogenous GSH through hepatic glutathione redox cycle can respond well to enhanced hepatic lipid peroxidation at an early stage of liver injury but not enough to enhanced hepatic lipid peroxidation at a progressed stage of liver injury.

Alanine Transaminase↗
PubMed1990

Role of glutathione in vanadate reduction in young and mature rats: evidence for direct participation of glutathione in vanadate inactivation.

The influence of renal glutathione content, modulated by the glutathione synthesis inhibitor buthionine sulphoximine or by glutathione infusion, on the polyuric and natriuretic effects of i.v. administered vanadate was investigated in 20- and 55-day-old rats. The modulation of renal glutathione content led to significant changes in urine volume and sodium excretion, independently of age. A decrease in the renal glutathione level led to intensification and prolongation of the diuretic effects of vanadate in 55-day-old animals. Treatment with glutathione abolished and treatment with buthionine sulphoximine increased the polyuric effect of vanadate. These observations indicate a role for renal glutathione in vanadate inactivation. Age-dependent differences in the polyuric and natriuretic effectiveness of vanadate are caused by differences in renal glutathione content during maturation of the kidney.

Aging↗
PubMed1997

Lipopolysaccharide-mediated hepatic glutathione depletion and progressive mitochondrial damage in mice: protective effect of glutathione monoethyl ester.

Overproduction of reactive oxygen intermediates (ROI) may have an important role in the pathophysiology of lipopolysaccharide-mediated liver-injury. This study examined the role of cytosolic and mitochondrial glutathione in protecting hepatocytes from oxidative stress during exposure to lipopolysaccharide. In addition, the possible participation of changes of inner mitochondrial membrane permeability in lipopolysaccharide-induced hepatotoxicity was investigated. The changes of hepatic glutathione content following lipopolysaccharide challenge (2 mg/kg) were measured in mice by reverse-phase high-performance liquid chromatography. Glutathione depletion and a glutathione-rich state were produced by intraperitoneal administration of a specific inhibitor of gamma-glutamyl cysteine synthetase, buthionine sulfoximine (3 mmol/kg), and by administration of glutathione monoethyl ester (10 mmol/kg), respectively. Intracellular ROI generation and the mitochondrial membrane potential were quantified by flow cytometry. Changes of inner mitochondrial membrane permeability in hepatocytes were assessed by radioactive sucrose entrapment. There was increased production of ROI along with depletion of cellular and mitochondrial glutathione in the liver after lipopolysaccharide administration. There was also a change of inner mitochondrial membrane permeability in hepatocytes, with the loss of coupled functions. Buthionine sulfoximine decreased the hepatic antioxidant capacity, worsened mitochondrial function, and reduced the survival rate of the mice. In contrast, glutathione monoethyl ester improved all of these parameters. Glutathione may have an important role in cellular defenses against lipopolysaccharide-induced liver damage in mice, and excessive oxidative stress may precipitate the mitochondrial membrane permeability transition in hepatocytes and lead to cell death.

Alanine Transaminase↗