Plasma Glutathione Concentrations Research Articles

Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of β-casein: results from a randomized, cross-over clinical trial.

This study reports the plasma glutathione concentrations in a double-blind, randomized, controlled, 2 × 2 cross-over study in which healthy participants consumed conventional milk (2 × 250 mL per day) containing both A1 and A2 types of β-casein, or milk containing only A2 type β-casein. Beta-casomorphin-7 (BCM-7), a peptide uniquely derived from the A1 type of β-casein, was previously reported to downregulate glutathione expression in human gut epithelial and neuronal cell lines by limiting cysteine uptake. The current human study demonstrates that consumption of milk containing only A2 β-casein was associated with a greater increase in plasma glutathione concentrations compared with the consumption of milk containing both β-casein types, and did not increase plasma BCM-7 concentrations compared with the washout diet in the study participants. Thus, milk containing only A2 β-casein and not A1 β-casein has the potential to promote the production of the antioxidant glutathione in humans.Clinical Trial RegistrationClinicalTrials.gov; identifier: NCT02406469 Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-016-0201-x) contains supplementary material, which is available to authorized users.

Amelioration of L-Dopa-Associated Dyskinesias with Triterpenoic Acid in a Parkinsonian Rat Model.

Levo-Dopa (L-Dopa) is widely used for the oral treatment of Parkinson's disease. However, chronic treatment with L-Dopa produces abnormal involuntary movements (AIMs) known as dyskinesias. In this study, commercially available oleanolic acid (OA) that has been previously shown to ameliorate the toxic effects of 6-hydroxydopamine (6-OHDA) in preconditioning studies was used to treat AIMs in a rat model for Parkinson's disease. The forelimb-use asymmetry test was used to measure Parkinson's disease-associated motor impairment. AIMs were measured after 21 days of L-Dopa administration. Glutathione levels were measured in blood, and catalase levels were measured in the substantia nigra and striatum of both the left and right hemispheres. We found that L-Dopa alone as well as L-Dopa and OA combination treatment attenuated the limb-use asymmetry caused by the unilateral injection of 6-OHDA. Chronic L-Dopa administration produced AIMs which were attenuated by treatment with OA. Catalase concentration decreased significantly in the striatum but not in the substantia nigra of the lesioned hemisphere. L-Dopa alone as well as the combined L-Dopa and OA treatment ameliorated the effects of 6-OHDA on catalase concentration. However, intervention with L-Dopa alone as well as with L-Dopa and OA did not affect plasma glutathione concentration. These results suggest that OA administration enhances the effect of catalase on reactive oxygen species following 6-OHDA injection. OA may provide possibilities as an adjunct treatment to prevent or attenuate the development of AIMs following chronic L-Dopa treatment in Parkinson's disease.

Avenanthramide supplementation attenuates eccentric exercise-inflicted blood inflammatory markers in women.

Rigorous exercise is known to generate reactive oxygen species (ROS) and inflict inflammatory response. The present study investigated whether dietary supplementation of avenanthramides (AVA) in oats would increase antioxidant protection and reduce inflammation in humans after an acute bout of eccentric exercise. Young women (age 18-30 years, N = 16) were randomly divided into two groups in a double-blinded fashion, receiving two cookies made of oat flour providing 9.2 mg AVA (AVA) or 0.4 mg AVA (Control, C) each day for 8 weeks. Before and after the dietary regimen each group of subjects ran downhill (DR) on a treadmill at -9% grade for 1 h at a speed to elicit 75% of maximal heart rate. Blood samples were collected at rest, immediately and 24 h post-DR. Before dietary supplementation plasma creatine kinase activity and tumor necrosis factor (TNF)-α concentration were increased immediately after DR (P < 0.05), whereas neutrophil respiratory burst (NRB) was elevated 24 h post-DR (P < 0.05). CK and TNF-α response to DR was abolished during post-supplementation tests in both AVA and C groups, whereas NRB was blunted only in AVA but not in C. Plasma interleukin-6 level and mononuclear cell nuclear factor (NF) κB activity were not affected by DR either before or after dietary supplementation, but were lowered 24 h post-DR in AVA versus C (P < 0.05). Both groups increased plasma total antioxidant activity following 8-week dietary regimen (P < 0.05), whereas only AVA group increased resting plasma glutathione (GSH) concentration (P < 0.05), decreased glutathione disulfide response to DR, and lowered erythrocyte GSH peroxidase activity (P < 0.05). Our data of pre- and post-supplementation difference reflect an interaction between repeated measure effect of eccentric exercise and AVA in diet. Long-term AVA supplementation can attenuate blood inflammation markers, decrease ROS generation and NFkB activation, and increased antioxidant capacity during an eccentric exercise bout.

Correlation of Acetaminophen, Ethanol, and Cocaine Use, Plasma Glutathione Concentrations, and Diet with Hepatotoxicity

Correlation of Acetaminophen, Ethanol, and Cocaine Use, Plasma Glutathione Concentrations, and Diet with Hepatotoxicity

Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress

BackgroundVitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system.ObjectiveThe purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress.DesignFour-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group), a vitamin B6-deficient diet (as a B6-deficient group), or a B6-supplemented diet (a pyridoxine-HCl-free diet supplemented with 14 mg/kg of pyridoxine-HCl, as a B6 supplement group) for 28 days. Homocysteine thiolactone was then added to drinking water in three groups for 21 days to induce oxidative stress. At the end of the study, mice were sacrificed by decapitation and blood and liver samples were obtained.ResultsMice with vitamin B6-deficient diet had the highest homocysteine concentration in plasma and liver among groups. Significantly increased hepatic malondialdehyde levels were observed in the vitamin B6-deficient group. Among homocysteine-treated groups, mice with vitamin B6-deficient diet had the highest plasma glutathione concentration and relatively lower hepatic glutathione concentration. The glutathione peroxidase activities remained relatively stable in plasma and liver whether vitamin B6 was adequate, deficient, or supplemented.ConclusionsMice with deficient vitamin B6 intakes had an aggravate effect under homocysteine-induced oxidative stress. The vitamin B6-deficient status seems to mediate the oxidative stress in connection with the redistribution of glutathione from liver to plasma, but not further affect glutathione-related enzyme activities in mice with homocysteine-induced oxidative stress.

Alteration in antioxidants level and lipid peroxidation of patients with neurodegenerative diseases {Alzheimer′s disease and Parkinson disease}

Objective: To assess the level of oxidative stress (OS) and the antioxidants that play a prominent role in OS of neurodegenerative diseases; also to test the hypothesis that OS is associated with neuronal degeneration in patients with neurodegenerative diseases {Parkinson's Disease (PD) and Alzheimer's Disease (AD)}. Materials and Methods: A total of 28 AD, 42 PD patients and 42 healthy controls aged 60-80 yrs were recruited for the study. Plasma total antioxidant status (TAS), erythrocyte malondialdehyde (MDA) and glutathione (GSH) concentrations were determined. Erythrocyte antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glucose-6-phosphate dehydrogenase (G6PD) were measured by using standard methods. Results: Plasma TAS was significantly reduced (P < 0.05) in AD and PD subjects when compared with the controls. Erythrocyte antioxizdant enzymes activities of SOD, GSH-Px, CAT and activity of G6PD were significantly reduced (P < 0.01) in AD and PD when compared with that of controls. However, erythrocyte level of MDA in AD and PD subjects were significantly increased (P < 0.01) compared to the controls. Erythrocyte GSH level was significantly reduced (P < 0.01) in AD subjects and (P < 0.05) in PD subjects when compared with the control. Strong significant (P < 0.01) correlation was obtained between the marker of OS (MDA) and SOD among PD and AD patients. Conclusion: The present study reveals elevated OS and strong correlation between SOD and MDA. This indicates that reduced SOD plays a prominent role in the increase of OS in neuronal degeneration.

Effect of Lutein on L-NAME-Induced Hypertensive Rats

We investigated the antihypertensive effect of lutein on NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Daily oral administration of L-NAME (40 mg/kg)-induced a rapid progressive increase in mean arterial pressure (MAP). L-NAME significantly increased MAP from the first week compared to that in the control and reached 193.3±9.6 mmHg at the end of treatment. MAP in the lutein groups was dose-dependently lower than that in the L-NAME group. Similar results were observed for systolic and diastolic blood pressure of L-NAME-induced hypertensive rats. The control group showed little change in heart rate for 3 weeks, whereas L-NAME significantly reduced heart rate from 434±26 to 376±33 beats/min. Lutein (2 mg/kg) significantly prevented the reduced heart rate induced by L-NAME. L-NAME caused hypertrophy of heart and kidney, and increased plasma lipid peroxidation four-fold but significantly reduced plasma nitrite and glutathione concentrations, which were significantly prevented by lutein in a dose-dependent manner. These findings suggest that lutein affords significant antihypertensive and antioxidant effects against L-NAME-induced hypertension in rats.

Effects of hydrogen peroxide on diazepam and xylazine sedation in chicks

Oxidative stress may cause various neuronal dysfunctions and modulate responses to many centrally acting drugs. This study examines the effects of oxidative stress produced by hydrogen peroxide (H2O2) on sedation induced by diazepam or xylazine as assessed in 7–14 day-old chicks. Day-old chicks were provided with either plane tap water (control group) or H2O2 in tap water as 0.5% v/v drinking solution for two weeks in order to produce oxidative stress. Spectrophotometric methods were used to determine glutathione and malondialdehyde concentrations in plasma and whole brain. Drug-induced sedation in the chicks was assessed by monitoring the occurrence of signs of sedation manifested as drooping of the head, closed eyelids, reduced motility or immotility, decreased distress calls, and recumbency. The latency to onset of sedation and its duration were also recorded. H2O2 treatment for two weeks significantly decreased glutathione and increased malondialdehyde concentrations in plasma and whole brain of the chicks on days 7, 10 and 14 as compared with respective age-matched control groups. H2O2 decreased the median effective doses of diazepam and xylazine for the induction of sedation in chicks by 46% and 63%, respectively. Injection of diazepam at 2.5, 5 and 10 mg/kg, i.m. or xylazine at 2, 4 and 8 mg/kg, i.m. induced sedation in both control and H2O2-treated chicks in a dose dependent manner, manifested by the above given signs of sedation. H2O2 significantly decreased the latency to onset of sedation in chicks treated with diazepam at 5 and 10 mg/kg, increased the duration of sedation and prolonged the total recovery time in comparison with respective non-stressed control chicks. A similar trend occurred with xylazine in the H2O2-treated chicks, though the differences from control counterparts did not attain the statistical significance, except for the recovery time of the lowest dose of the drug. The data suggest that H2O2-induced oxidative stress sensitizes the chicks to the depressant action of the sedatives diazepam and xylazine. Further studies are needed to examine the potential role of oxidative stress in modulating the actions of therapeutic agents on the brain.

Effect of acetaminophen on the progression of renal damage in adenine induced renal failure model rats

AimsAcetaminophen is a safe antipyretic and analgesic drug within the clinically recommended dosage range, but overdose can cause fatal liver and or kidney damage. Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect via inhibition of cyclooxygenase, which also results in a reduction of renal blood flow. Therefore, the use of NSAIDs in pain treatment for chronic kidney disease (CKD) patients is of particular concern. Acetaminophen lacks the anti-inflammatory and anti-coagulatory properties of the NSAIDs. In this study, we investigate whether acetaminophen has an impact on the progression of renal failure. Main methodsAcetaminophen (150mg/kg/day or 750mg/kg/day) or indomethacin (5mg/kg/day) was orally administered to adenine-induced chronic renal failure model rats for 4weeks. The plasma concentrations of acetaminophen and its metabolites were measured during the treatment period; renal function and oxidative stress in the rats were also monitored. Key findingsIndomethacin significantly decreased the survival rate of renal failure model rats. In contrast, both low (150mg/kg) and high (750mg/kg) doses of acetaminophen improved the survival rate. The progression of renal failure was attenuated by acetaminophen (750mg/kg) after administration for 2weeks. The metabolites of acetaminophen were found to accumulate in plasma. Plasma glutathione concentration had significantly recovered after acetaminophen administration. SignificanceAcetaminophen has no effect on the progression of renal damage in adenine-induced renal failure model rats. This result is in part due to acetaminophen's antioxidant activity. These results suggest that acetaminophen is a suitable analgesic agent for treating CKD patients.

Effects of Obesity on Serum Concentration of Methylation and Oxidative/ Nitrosative Stress Metabolites Following DMBA Treatment of Female Zucker Rats

Obesity has been an epidemic in the United States for more than two decades. Studies in humans and animals have suggested that obesity is major risk for breast cancer development. It is well established that increased oxidative stress and changes in DNA can contribute to carcinogenesis. Low molecular weight antioxidant glutathione plays exceptional role in protection of cells from oxidative damage. S-adenosylmethionine, a metabolite of amino acid methionine, is a key methyl group donor for numerous of reaction including DNA. The main objective of this experiment was to investigate the effects of obesity on serum concentration of oxidative stress markers and products of oxidative damage and methylation-reaction donor S-adenosylmethionine following 7,12-dimethylbenz(a) anthracene (DMBA) treatment. Obese and lean female Zucker rats were maintained on a regular chow diet for two weeks. All rats were orally gavaged at age 50 days with 65 mg/kg DMBA. Twenty four hours after DMBA treatment, all rats were sacrificed and serum was collected. Highly sensitive HPLC method with CoulArray electrochemical detector was utilized for determination of thiols, 3-NT and SAM, SAH, and Adenosine. The obese rats had a 40% increased level of oxidized glutathione (P=0.007), decreased GSH/GSSG ratio (P=0.003), increased SAH (P=0.025) and also a 30% increased level of Ado (P=0.005) compared to lean rats. The lean animals showed a slightly higher (20%) concentration of SAM and 50% higher SAM: SAH ratio (P=0.02) compared to obese animals. These results showed that by using DMBA-induced mammary tumor development obesity can contribute to a significant imbalance in oxidative/reduction homeostasis in serum and depression in serum SAM: SAH known as methylation ratio, and increase SAH level, known as potent inhibitor methylases. These data suggest that changes plasma concentrations of glutathione, SAH and SAM reflect intracellular changes that possibly can contribute to carcinogenesis.

Enteral nutrition supplemented with l-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection

ObjectiveTo evaluate the effect of enteral nutrition (EN) supplemented with l-glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis. MethodsThirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation. ResultsThere were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0–47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations. ConclusionsThe EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters.

Metabolic origin of hypovitaminosis C in acutely hospitalized patients

Objective Recent studies have indicated a high prevalence of hypovitaminosis C in acutely hospitalized patients. It is unclear whether hypovitaminosis C in this setting represents deficiency or tissue redistribution of the vitamin as part of the acute-phase response. Methods We administered vitamin C for 1 wk to acutely hospitalized, but not critically ill patients with hypovitaminosis C, on the assumption that a large increase in plasma and mononuclear leukocyte vitamin C concentrations, a decrease in metabolic markers of oxidative stress, or an improvement in psychologic mood state would implicate the initial condition as nutritional deficiency rather than tissue redistribution. Results Vitamin C administration increased plasma and mononuclear leukocyte vitamin C concentrations from subnormal (16.3 ± 12.4 μmol/L and 6.5 ± 5.5 mmol/L, respectively) to normal (71.0 ± 30.9 μmol/L, P < 0.0001, and 8.2 ± 6.8 mmol/L, P < 0.015); the mood disturbance score improved by 33% ( P < 0.008). There was no increase in plasma glutathione concentrations or a reduction in plasma or mononuclear leukocyte malondialdehyde concentrations. An inverse relation was observed between plasma C-reactive protein and plasma vitamin C concentrations ( P = 0.006). Conclusion Although associated with systemic inflammation, the metabolic features of hypovitaminosis C in acutely hospitalized, non-critically ill patients are more consistent with deficiency than with tissue redistribution.

Circulating and muscle glutathione turnover in human endotoxaemia

Patients with septic shock have high plasma glutathione concentrations, whereas intracellular concentrations in erythrocytes and muscle are low. In the present study, we investigated the temporal pattern of glutathione status and glutathione kinetics in healthy volunteers during the initial phase of sepsis using a human endotoxin model. The present study was a descriptive pilot study in healthy male volunteers (n=8) before and after an endotoxin challenge. The glutathione status was determined in plasma and whole blood at baseline and hourly for 4 h after intravenous endotoxin injection and in skeletal muscle at baseline and at 2 and 4 h after endotoxin injection. In plasma, the concentration of total glutathione decreased 24% (P<0.05) at 3 h after endotoxin injection and 32% (P<0.001) at 4 h. In whole blood and skeletal muscle, the concentrations of both GSH and total glutathione as well as the redox status remained unaltered during the initial 4 h after the endotoxin challenge. The FSR (fractional synthesis rate) of glutathione in whole blood was 38+/-20%/day before and 59+/-22%/day 4 h after the endotoxin challenge (P=0.088) and in skeletal muscle this was 41+/-25 and 46+/-18%/day (P=0.68) respectively. During the initial phase of sepsis, as represented by an intravenous endotoxin challenge to healthy volunteers, plasma concentrations of total glutathione decreased, whereas glutathione status and synthesis rate in skeletal muscle and whole blood remained unaltered. However, due to the variation in the synthesis measurements, larger studies are needed to confirm these findings.

Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women

Background:Glutathione plays various protective roles in the human body. Vitamin B-6 as pyridoxal-5′-phosphate (PLP) is required as the coenzyme in the formation of glutathione precursors. Despite this obligatory role of PLP, previous studies from this laboratory showed that vitamin B-6 deficiency caused elevated glutathione concentrations in rat liver and human plasma. Objective:Our aim was to determine the effect of marginal vitamin B-6 deficiency (plasma PLP 20–30 nmol/L) on the rate of red blood cell (RBC) glutathione synthesis. Design:We measured plasma and RBC glutathione concentrations and the fractional and absolute synthesis rates of RBC glutathione using the stable-isotope-labeled glutathione precursor [1,2-13C2]glycine in 13 healthy volunteers aged 21–39 y. Results:Dietary vitamin B-6 restriction did not significantly affect the glutathione concentration in plasma (6.9 ± 1.9 compared with 6.7 ± 1.1μmol/L) or RBCs (2068 ± 50 compared with 2117 ± 48μmol/L). For RBC glutathione, the mean fractional synthesis rates were 54 ± 5%/d and 43 ± 4%/d (P = 0.10), and the absolute synthesis rates were 1116 ± 100 and 916 ± 92μmol · L−1 · d−1 (P = 0.14) before and after vitamin B-6 restriction, respectively. Conclusions:Marginal vitamin B-6 deficiency tended to decrease mean RBC glutathione synthesis with no effect on RBC glutathione concentration, but the responses varied widely among individuals. Because the cysteine concentration in plasma and RBC did not change during vitamin B-6 restriction, we conclude that the effects of marginal vitamin B-6 deficiency on glutathione synthesis are not caused by altered precursor concentrations.

Folate‐independent remethylation of homocysteine is increased by dietary egg white protein

Proper maintenance and regulation of methyl group and homocysteine (hcy) metabolism is essential for optimization of health. Methyl deficiency and/or elevations in plasma hcy concentrations have been associated with numerous pathologies, such as vascular disease. It is important to identify dietary components that positively impact these metabolic pathways; thus, we examined dietary protein sources with varying sulfur amino acid content. Rats were fed either a casein or egg white protein (20%) diet for 2 wk after which half the rats in each group were fed folate‐deficient diets for 4 wk. Compared to casein, egg white protein resulted in: (1) elevated hepatic betaine‐hcy S‐methyltransferase activity, responsible for folate‐independent hcy remethylation; (2) increased hepatic activity of glycine N‐methyltransferase, a key methyl group regulatory protein; and (3) reduced plasma glutathione concentrations. Moreover, folate deficiency was without affect on plasma hcy levels in the egg white group. In a parallel study, soy protein did not differ from casein with respect to altering methyl group and hcy metabolism. In conclusion, dietary egg white protein appears to promote hcy remethylation at the expense of catabolism via transsulfuration. These findings may be attributed to the greater met‐cys content of egg white protein compared to casein and soy (Support: Amer. Egg Board, Egg Nutr. Center, IA Egg Council).

Olive Phenolics Increase Glutathione Levels in Healthy Volunteers

Several in vitro and in vivo studies have shown that olive phenols exert potent biological activities including, but not limited to, antioxidant actions. These activities are shared by phenols found in olives, olive oil, and olive mill wastewater (OMWW). The aim of this study was to investigate whether a commercially available OMWW preparation could influence some parameters of oxidative status in healthy human volunteers. Ninety-eight healthy subjects with normal body weight were recruited, and 5 mL of blood was drawn from their antecubital vein after an overnight fast of at least 12 h. After this, subjects were asked to ingest 2 mL of a commercially available OMWW preparation. Another 5 mL of blood was drawn 1 h after ingestion of the preparation. Plasma antioxidant capacity and total and reduced glutathione were measured. No difference in plasma antioxidant capacity was observed between baseline and 1 h after the ingestion of the extract. Conversely, a significant increase in total plasma glutathione concentration was measured. This increase involved both the reduced and oxidized forms of glutathione; hence, their ratio was unaffected by the treatment. The observed effects of OMWW on glutathione levels might be governed by the antioxidant response element (ARE)-mediated increase in phase II enzyme expression, including that of gamma-glutamylcysteine ligase and glutathione synthetase. Future studies on groups of individuals who may benefit from an increase in their glutathione levels, for example, the elderly, will further elucidate the biological activities of this formulation.

The Effect of Glutathione Modulation on the Concentration of Homocysteine in Plasma of Rats

Elevated plasma homocysteine concentration in humans is associated with increased risk of arteriosclerosis and ischaemic heart disease. We studied whether the plasma homocysteine concentration could be changed by administration of drugs that modulate the concentration of glutathione in both plasma and tissue. Male wistar rats received reduced glutathione (0.5 mmol/kg), N-acetylcysteine (0.5 mmol/kg), L-buthionine-[S,R]-sulfoximine (2 mmol/kg) or Ringer acetate intravenously. Twenty min. later an arterial blood sample was drawn for the measurement of homocysteine and other thiols in the plasma. The thiols were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The total homocysteine concentration in plasma of fasted rats was 6.1±0.5 μM. Intravenous administration of reduced glutathione or N-acetylcysteine reduced the homocysteine concentration in plasma significantly by 51% to 3.0±0.3 μM and 63% to 2.2±0.2 μM, respectively (P<0.05). In contrast, L-buthionine-[S,R]-sulfoximine increased the concentration of homocysteine by 41% to 8.6±0.6 μM (P<0.05). The glutathione concentration in plasma was 19.5±1.9 μM in controls and was unchanged by N-acetylcysteine administration. Reduced glutathione increased plasma glutathione to 379.7±22.9 μM (P<0.05), whereas L-buthionine-[S R]-sulfoximine lowered the plasma glutathione concentration to 5.3±0.4 μM. Homocysteine was negatively correlated to the glutathione (r=−0.399, P<0.01) and the cysteine (r=−0.52, P<0.01) concentrations in plasma. Our conclusion is that modulation of the glutathione levels influences the concentration of homocysteine in plasma of rats.

Quantification of plasma reduced glutathione, oxidized glutathione and plasma total glutathione in healthy cats.

Glutathione is an important intracellular tripeptide with multiple functions. Abnormal glutathione metabolism is thought to play an important role in various diseases of cats. However, no data regarding concentration of plasma glutathione are available for domestic cats. This study discusses the development of a rapid, simple high pressure liquid chromatography method for measurement of reduced glutathione (GSH), oxidized glutathione (GSSH) and total glutathione (GSHt) in plasma, for the purpose of establishing baseline data for future studies. The mean concentrations of GSH, GSSH and GSHt were 4.51+/-1 microM; 19.44+/-3.79 microM (expressed as GSH equivalent) and 23.59+/-3.89 microM, respectively. This is the first report of plasma glutathione concentrations in this species.

Acetaminophen Usage Patterns and Concentrations of Glutathione and γ‐Glutamyl Transferase in Alcoholic Subjects

To determine if subjects with chronic alcoholism are predisposed to acetaminophen-induced hepatotoxicity, and to determine the contributing factors. Prospective cohort study. Community-based crisis intervention center. One hundred eighty-eight subjects who answered "yes" to at least one of the four questions on the CAGE (Cut down-Annoyed-Guilty-Eye-opener) questionnaire for identifying alcoholism, and 10 healthy volunteers (controls). A history, physical examination, urine toxicologic analysis, ethanol and drug therapy history, and venous blood samples were collected on all subjects. Venous blood was analyzed for a liver profile, prothrombin time, and total and oxidized glutathione concentrations. A significantly higher proportion of daily drinkers were regular daily users (29.2% [45/154] vs 11.8% [4/34], p=0.0497) as well as abusers (35.7% [55/154] vs 14.7% [5/34], p=0.0237) of acetaminophen compared with non daily drinkers. Alcoholic subjects with elevated gamma-glutamyl transferase (GGT >or= 51 U/L) levels had significantly lower median plasma glutathione concentrations (2.33 micromol/L, 95% confidence interval [CI] 1.74-2.69 micromol/L) compared with those of alcoholic subjects with normal GGT concentrations (5.97 micromol/L, 95% CI 4.39-7.03 micromol/L, p<0.0001) and healthy volunteers (6.59 micromol/L, 95% CI 4.79-9.65 micromol/L, p=0.0002). A significant inverse correlation was also noted between the GGT concentration and the plasma total glutathione concentration (r = -0.62, p<0.0001). None of the 188 subjects met all preset criteria for hepatotoxicity. Daily drinkers were more than twice as likely as non daily drinkers to be regular daily acetaminophen users and abusers. Alcoholic subjects with elevated GGT concentrations had significantly lower plasma total glutathione concentrations, and plasma total glutathione concentrations inversely correlated with GGT concentrations. Elevated GGT concentrations may be a clinical marker of depleted glutathione in alcoholic subjects. Acetaminophen-induced hepatotoxicity appears to be uncommon in alcoholic subjects, despite the 31.9% (60/188 patients) who took doses that are potentially hepatotoxic.

Oral branched‐chain amino acid supplementation improves the oxidized/reduced albumin ratio in patients with liver cirrhosis

Branched-chain amino acid (BCAA) supplementation improves hypoalbuminemia in decompensated cirrhotics. Recently, it was clarified that the ratio of oxidized albumin within total albumin rises with progression of liver cirrhosis. We conducted a feasibility study to investigate whether BCAA supplementation might improve this ratio. Seven cirrhotic patients (age: 70 +/-> 6 years; M/F = 4/3; etiology: hepatitis C in six and non-B/non-C hepatitis virus in one; Child-Pugh classification: A in six and B in one) were enrolled consecutively in this study in October 2004 to March 2005. Patients were given 4 g BCAA after each meal for 8 weeks. Serum total, oxidized and reduced albumin, plasma amino acids, glutathione, zinc, selenium, and lipid peroxide concentrations were measured every 2 weeks. Low total albumin, high oxidized albumin, and low reduced albumin levels were observed at entry. After 8 weeksBCAA supplementation, the ratio of oxidized albumin within total albumin decreased significantly and that of reduced albumin increased significantly (P < 0.05, respectively). Total albumin tended to rise and lipid peroxide concentrations tended to fall, but not significantly. BCAA supplementation improved the oxidized/reduced state of serum albumin. This intervention is effective to maintain the quality of serum albumin in cirrhotic patients.