DOCSLIB.ORG

Vitamin E Supplementation Restores Glutathione and Malondialdehyde to Normal Concentrations in Erythrocytes of Type 1 Diabetic Children

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Vitamin E Supplementation Restores Glutathione and Malondialdehyde to Normal Concentrations in Erythrocytes of Type 1 Diabetic Children Pathophysiology/Complications ORIGINAL ARTICLE Vitamin E Supplementation Restores Glutathione and Malondialdehyde to Normal Concentrations in Erythrocytes of Type 1 Diabetic Children SUSHIL K. JAIN, PHD ification of intracellular peroxides. Thus, ROBERT MCVIE, MD maintenance of glutathione level is pivotal TINEY SMITH, RN for cellular defense against oxidative injury and for cellular integrity (1,2). Hyperglycemia in diabetes can generate free radicals, hydrogen peroxide, and reac- tive ketoaldehydes by the auto-oxidation of OBJECTIVE — This study examined the relationship between cellular glutathione and vita- glucose or from glycated proteins (3–8). ␣ min E concentrations and the effect of vitamin E ( -tocopherol) supplementation on glutathione Many investigators have reported lower con- and lipid peroxidation product concentrations in the erythrocytes of type 1 diabetic patients. centrations of glutathione in the erythro- RESEARCH DESIGN AND METHODS — We obtained written informed consent to cytes, aorta, and lenses of diabetic patients participate in this study from diabetic patients (n = 29) and their age-matched nondiabetic sib- compared with healthy subjects (9–19), lings (n = 21) according to the guidelines of the Institutional Review Board on Human Exper- except for some studies that reported similar imentation. Diabetic patients were supplemented with a DL-␣-tocopherol (vitamin E) capsule glutathione concentrations (20). In addi- (100 IU/ orally) or placebo for 3 months in a double-blind clinical trial. Fasting blood samples tion, an increase in malondialdehyde con- were collected from each diabetic patient before the start of and after the 3 months of vitamin centration has been reported in erythrocytes E or placebo supplementation. Glutathione, malondialdehyde (which is a product of lipid per- and other tissues of diabetic animals and oxidation), and ␣-tocopherol were determined using high-performance liquid chromatography. patients (21–28). A total of 5 diabetic patients were excluded after randomization from the data analyses. Data Lower glutathione and elevated lipid were analyzed statistically using a paired Student’s t test to compare 12 diabetic patients tak- peroxidation concentrations are risk factors ing vitamin E with 12 diabetic patients receiving placebo supplementation and to compare dia- betic patients with healthy nondiabetic subjects. for the development of pathological states such as retinopathy, neuropathy, cataracts, RESULTS — Erythrocytes of diabetic patients had 21% higher (P Ͻ 0.001) malondialdehyde and atherosclerosis (1–3). Vitamin E has and 15% lower (P Ͻ 0.05) glutathione concentrations than healthy subjects. Vitamin E in ery- been proposed to be the major lipid-soluble throcytes had a significant correlation with the glutathione concentrations in the erythrocytes chain-breaking antioxidant and protects (r = 0.46, P Ͻ 0.02). Vitamin E supplementation increased glutathione concentrations by 9% biologic membranes from lipid peroxida- Ͻ Ͻ (P 0.01) and lowered concentrations of malondialdehyde by 23% (P 0.001) and of HbA1c tion (29). In vitro studies have shown that by 16% (P Ͻ 0.02) in erythrocytes of diabetic patients. No differences were evident in these reduced glutathione can protect against per- parameters before versus after placebo supplementation. oxidation of lipids in cytosolic and particu- late subfraction components of rat liver and CONCLUSIONS — Glutathione level is significantly related to vitamin E level, and sup- other tissues (29). In some experiments, plementation with vitamin E (100 IU/day) significantly increases glutathione and lowers lipid ␣ peroxidation and HbA concentrations in the erythrocytes of type 1 diabetic patients. this protection depends on membrane - 1c tocopherol (30), whereas in others it does Diabetes Care 23:1389–1394, 2000 not (31). Mechanisms that have been pro- posed to explain the glutathione effect include the removal of species that initiate lipid peroxidation, scavenging of radicals by educed glutathione is a major intra- reduced form, the oxidation of which can a glutathione-dependent protein (32), scav- cellular nonprotein sulfhydryl com- otherwise cause altered cellular structure enging of peroxy radicals by glutathione pound. Glutathione has many bio- and function (1,2). Glutathione is also a R (33), maintenance of membrane protein logic functions, including maintenance of cofactor for many enzymes such as glu- thiols by glutathione (34), the protection by membrane protein sulfhydryl groups in the tathione peroxidase, which catalyzes detox- glutathione and ␣-tocopherol of a glu- tathione S-transferase isozyme responsible From the Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, Louisiana. for the reduction of lipid hydroperoxides Address correspondence and reprint requests to Sushil K. Jain, PhD, Department of Pediatrics, Louisiana (35), and a glutathione-dependent protein State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130. E-mail: that recycles ␣-tocopherol from the ␣-toco- [email protected]. pheroxy radical (31). Received for publication 4 November 1999 and accepted in revised form 23 May 2000. Abbreviations: HPLC, high-performance liquid chromatography; TBA, thiobarbituric acid. In vivo studies in animal models have A table elsewhere in this issue shows conventional and Système International (SI) units and conversion shown inhibition of lipid peroxidation and factors for many substances. increased glutathione concentrations in the DIABETES CARE, VOLUME 23, NUMBER 9, SEPTEMBER 2000 1389 Vitamin E supplementation in diabetes ␣ Table 1—Age, duration of diabetes, HbA1c, glutathioine, malondialdehyde, and -tocopherol nondiabetic subjects (healthy siblings) were concentrations in erythrocytes of nondiabetic subjects and diabetic patients also enrolled to serve as healthy control subjects, and data from healthy control subjects were used for the cross-sectional Diabetic patients Nondiabetic subjects P aspect of the study. Fasting blood samples n 29 21 — were collected into tubes with and without Age (years) 12.4 ± 0.7 10.9 ± 0.9 NS EDTA before and after the vitamin E or Duration of diabetes (years) 5.3 ± 0.7 — — placebo supplementation from each Ͻ Blood HbA1c (%) 8.44 ± 0.21 5.03 ± 0.14 0.001 patient. Erythrocytes were separated and Glutathione erythrocytes (µmol/g Hb) 5.8 ± 0.2 6.4 ± 0.2 Ͻ0.05 washed from the EDTA-treated blood (21). Malondialdehyde erythrocytes (nmol) All analyses were conducted immediately Per milliliter packed cell volume 1.46 ± 0.04 1.30 ± 0.04 Ͻ0.02 after blood collection. Per gram Hb 4.27 ± 0.13 3.67 ± 0.14 Ͻ0.03 Glutathione was determined using Per micromole total lipid 0.29 ± 0.008 0.24 ± 0.006 Ͻ0.01 high-performance liquid chromatography ␣-Tocopherol erythrocytes (nmol) (HPLC) with a Lichrosphere (EM Separation Per milliliter packed cell volume 4.38 ± 0.13 4.11 ± 0.13 NS Technology, Gibbstown, NJ) 100 NH2 col- Per gram Hb 12.88 ± 0.40 12.00 ± 0.40 NS umn, a gradient system using buffer A (80% Per micromole total lipid 0.87 ± 0.03 0.75 ± 0.03 NS methanol and 20% water) and buffer B (4 mol/l acetate, pH 4.5 in 64% methanol- Data are means ± SEM unless otherwise indicated. Note significant differences in the blood HbA1c and in glu- tathione and malondialdehyde erythrocytes concentrations in erythrocytes of diabetic patients versus healthy water), and a ultraviolet/visible detector set nondiabetic subjects. Details of statistical analyses are discussed in RESEARCH DESIGN AND METHODS. at 365 nm (40). Vitamin E as ␣-tocopherol was measured by HPLC (23). Freshly obtained erythrocytes were stored in 2% liver and heart of guinea pigs after dietary RESEARCH DESIGN AND pyrogallol in ethanol at Ϫ70°C. All samples supplementation (150 mg/kg diet) with vit- METHODS — Informed written con- were analyzed within 1 month of storage amin E (36,37). Similarly, subcutaneous sent of all patients was obtained in accor- using a reverse-phase C-18 column (Waters, treatment with vitamin E (10 mg/100 kg dance with the protocol approved by the Milford, MA), a 95% methanol solvent sys- body wt) increased glutathione concentra- Institutional Review Board on Human tem, and a uv/vis detector set at 292 nm tions and reduced lipid peroxidation in Experimentation. No specific criterion was (23). Lipid peroxidation was determined by renal tissues of adult rats (38). Increases in used for inclusion or exclusion of patients measuring malondialdehyde, which is an glutathione level were reported in the ery- in this study except that patients who had end product of lipid peroxidation. Malondi- throcytes, aqueous humor, and lenses of other disorders such as sickle cell disease or aldehyde can react with thiobarbituric acid rabbits supplemented orally with 30 mg thyroid disorders or those taking other (TBA), and the concentration of malondi- vitamin E и dayϪ1 и kgϪ1 body wt for 10 or medications were excluded from the study. aldehyde-TBA complex was determined by 20 days (39). In humans, increases in glu- All patients agreed to participate in this its separation with an HPLC system (Waters) tathione level were shown in the erythro- study. Diabetic patients who were invited and a uv/vis detector set at 532 nm (41). cytes and aqueous humor after high-dose and agreed to participate in this study were Variation in the assay of the same sample on oral supplementation of 1,000 IU vitamin E asked to come to the clinic after overnight different days was Ͻ7%. for 10 days in 20 subjects hospitalized
Load more

Recommended publications
  • Mechanistic Insights on the Reduction of Glutathione Disulfide by Protein Disulfide Isomerase
    Mechanistic insights on the reduction of glutathione disulfide by protein disulfide isomerase Rui P. P. Nevesa, Pedro Alexandrino Fernandesa, and Maria João Ramosa,1 aUnidade de Ciências Biomoleculares Aplicadas, Rede de Química e Tecnologia, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal Edited by Donald G. Truhlar, University of Minnesota, Minneapolis, MN, and approved May 9, 2017 (received for review November 22, 2016) We explore the enzymatic mechanism of the reduction of glutathione of enzymes, which are responsible for the reduction and isomer- disulfide (GSSG) by the reduced a domain of human protein disulfide ization of disulfide bonds, through thiol-disulfide exchange. isomerase (hPDI) with atomistic resolution. We use classical molecular dynamics and hybrid quantum mechanics/molecular mechanics cal- Structure and Function of PDI culations at the mPW1N/6–311+G(2d,2p):FF99SB//mPW1N/6–31G(d): Human protein disulfide isomerase (hPDI) is a U-shaped enzyme FF99SB level. The reaction proceeds in two stages: (i) a thiol-disulfide with 508 residues. Its tertiary structure is composed of four exchange through nucleophilic attack of the Cys53-thiolate to the thioredoxin-like domains (a, b, b′,anda′) and a fifth tail-shaped c GSSG-disulfide followed by the deprotonation of Cys56-thiol by domain (Fig. 1) (14, 15). The maximum activity of hPDI is observed Glu47-carboxylate and (ii) a second thiol-disulfide exchange between when all domains of PDI contribute synergistically to its function (16). the Cys56-thiolate and the mixed disulfide intermediate formed in Similar to thioredoxin, the a and a′ domains have a catalytic the first step.
    [Show full text]
  • Degradation of Glutathione in Plant Cells
    Degradation of Glutathione in Plant Cells: Evidence against the Participation of a y-Glutamyltranspeptidase Reinhard Steinkamp and Heinz Rennenberg Botanisches Institut der Universität zu Köln, Gyrhofstr. 15, D-5000 Köln 41, Bundesrepublik Deutschland Z. Naturforsch. 40c, 29 — 33 (1985); received August 31/October 4, 1984 Tobacco, Glutathione Catabolism, y-Glutamylcysteine, y-Glutamyltranspeptidase, y-Glutamyl- cyclotransferase When y-glutamyltranspeptidase activity in tobacco cells was measured using the artificial substrate y-glutamyl-/?-nitroanilide, liberation of p-nitroaniline was not reduced, but stimulated by addition of glutathione. Therefore, glutathione was not acting as a donator, but as an acceptor of y-glutamyl moieties in the assay mixture, suggesting that y-glutamyltranspeptidase is not participating in degradation of glutathione. Feeding experiments with [^S-cysJglutathione sup­ ported this conclusion. When tobacco cells were supplied with this peptide as sole sulfur source, glutathione and y-glutamylcysteine were the only labelled compounds found inside the cells. The low rate of uptake of glutathione apparently prevented the accumulation of measurable amounts of radioactivity in the cysteine pool. A y-glutamylcyclotransferase, responsible for the conversion of y-glutamylcysteine to 5-oxo-proline and cysteine was found in ammonium sulfate precipitates of tobacco cell homogenates. The enzyme showed high activities with y-glutamylmethionine and y-glutamylcysteine, but not with other y-glutamyldipeptides or glutathione. From these and previously published experiments [(Rennenberg et al., Z. Naturforsch. 3 5 c, 70 8 -7 1 1 (1980)], it is concluded that glutathione is degraded in tobacco cells via the following pathway: y-glu-cys- gly —> y-glu-cys ->• 5-oxo-proline -* glu. Introduction the cysteine conjugate by the action of a y-gluta­ myltranspeptidase (Fig.
    [Show full text]
  • Sulfhydryl Reduction of Methylene Blue with Reference to Alterations in Malignant Neoplastic Disease
    Sulfhydryl Reduction of Methylene Blue With Reference to Alterations in Malignant Neoplastic Disease Maurice M. Black, M. D. (From the Department of Biochemistry, New York Medical College, New York 29, N. t;., and the Brooklyn Cancer Institute, Brooklyn 9, N. Y.) (Received for publication May 8, 1947) A significant decrease in methylene blue re- reactivity is less than half that of the cysteine. It is ducing power of plasma from patients with malig- noteworthy also that the resultant leuco mixture nant neoplastic disease was previously reported did not revert back to colored methylene blue on (1). At that time it was suggested that change in a cooling, as was the case with methylene blue re- reducing group of the albumin molecule was a duction by plasma. likely source of this alteration. Similar conclusions Similar relationships were investigated between were reported also by Savignac and associates (7) cysteine and different concentrations of methylene as the result of analogous studies. blue. As seen in Fig. 2, similar curves are obtained, In an attempt to evaluate the effect of the sulf- but the position of the curve on the graph varies hydryl group on the reduction of methylene blue, a with the concentration of the methylene blue used. study was undertaken with various compounds of It should be noted that there is no appreciable known -SH and S-S structures. In addition, an difference in the reducing time of methylene blue attempt was made to establish a standard method on varying the concentrations between 0.10 per of calibration of various lots of methylene blue, so cent and 0.2 per cent, although 0.08 per cent shows that more uniform results would be possible in the a decided difference.
    [Show full text]
  • A Review of Dietary (Phyto)Nutrients for Glutathione Support
    nutrients Review A Review of Dietary (Phyto)Nutrients for Glutathione Support Deanna M. Minich 1,* and Benjamin I. Brown 2 1 Human Nutrition and Functional Medicine Graduate Program, University of Western States, 2900 NE 132nd Ave, Portland, OR 97230, USA 2 BCNH College of Nutrition and Health, 116–118 Finchley Road, London NW3 5HT, UK * Correspondence: [email protected] Received: 8 July 2019; Accepted: 23 August 2019; Published: 3 September 2019 Abstract: Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
    [Show full text]
  • Muscle Wasting and Aging: Experimental Models, Fatty Infiltrations, and Prevention Thomas Brioche, Allan Pagano, Guillaume Py, Angèle Chopard
    Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention Thomas Brioche, Allan Pagano, Guillaume Py, Angèle Chopard To cite this version: Thomas Brioche, Allan Pagano, Guillaume Py, Angèle Chopard. Muscle wasting and aging: Experi- mental models, fatty infiltrations, and prevention. Molecular Aspects of Medicine, Elsevier, 2016,32 p. 10.1016/j.mam.2016.04.006. hal-01837630 HAL Id: hal-01837630 https://hal.archives-ouvertes.fr/hal-01837630 Submitted on 28 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - ShareAlike| 4.0 International License Accepted Manuscript Title: Muscle wasting and aging: experimental models, fatty infiltrations, and prevention Author: Thomas Brioche, Allan F. Pagano, Guillaume Py, Angèle Chopard PII: S0098-2997(15)30021-2 DOI: http://dx.doi.org/doi: 10.1016/j.mam.2016.04.006 Reference: JMAM 642 To appear in: Molecular Aspects of Medicine Received date: 19-12-2015 Revised date: 13-4-2016 Accepted date: 13-4-2016 Please cite this article as: Thomas Brioche, Allan F. Pagano, Guillaume Py, Angèle Chopard, Muscle wasting and aging: experimental models, fatty infiltrations, and prevention, Molecular Aspects of Medicine (2016), http://dx.doi.org/doi: 10.1016/j.mam.2016.04.006.
    [Show full text]
  • Figure S1. Heat Map of R (Pearson's Correlation Coefficient)
    Figure S1. Heat map of r (Pearson’s correlation coefficient) value among different samples including replicates. The color represented the r value. Figure S2. Distributions of accumulation profiles of lipids, nucleotides, and vitamins detected by widely-targeted UPLC-MC during four fruit developmental stages. The colors indicate the proportional content of each identified metabolites as determined by the average peak response area with R scale normalization. PS1, 2, 3, and 4 represents fruit samples collected at 27, 84, 125, 165 Days After Anthesis (DAA), respectively. Three independent replicates were performed for each stages. Figure S3. Differential metabolites of PS2 vs PS1 group in flavonoid biosynthesis pathway. Figure S4. Differential metabolites of PS2 vs PS1 group in phenylpropanoid biosynthesis pathway. Figure S5. Differential metabolites of PS3 vs PS2 group in flavonoid biosynthesis pathway. Figure S6. Differential metabolites of PS3 vs PS2 group in phenylpropanoid biosynthesis pathway. Figure S7. Differential metabolites of PS4 vs PS3 group in biosynthesis of phenylpropanoids pathway. Figure S8. Differential metabolites of PS2 vs PS1 group in flavonoid biosynthesis pathway and phenylpropanoid biosynthesis pathway combined with RNA-seq results. Table S1. A total of 462 detected metabolites in this study and their peak response areas along the developmental stages of apple fruit. mix0 mix0 mix0 Index Compounds Class PS1a PS1b PS1c PS2a PS2b PS2c PS3a PS3b PS3c PS4a PS4b PS4c ID 1 2 3 Alcohols and 5.25E 7.57E 5.27E 4.24E 5.20E
    [Show full text]
  • Combined L-Citrulline and Glutathione Supplementation Increases The
    McKinley-Barnard et al. Journal of the International Society of Sports Nutrition (2015) 12:27 DOI 10.1186/s12970-015-0086-7 RESEARCH Open Access Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis Sarah McKinley-Barnard1, Tom Andre1, Masahiko Morita2 and Darryn S. Willoughby1* Abstract Background: Nitric oxide (NO) is endogenously synthesized from L-arginine and L-citrulline. Due to its effects on nitric oxide synthase (NOS), reduced glutathione (GSH) may protect against the oxidative reduction of NO. The present study determined the effectiveness of L-citrulline and/or GSH on markers indicative of NO synthesis in in vivo conditions with rodents and humans and also in an in vitro condition. Methods: In phase one, human umbilical vein endothelial cells (HUVECs) were treated with either 0.3 mM L-citrulline, 1 mM GSH (Setria®) or a combination of each at 0.3 mM. In phase two, Sprague–Dawley rats (8 weeks old) were randomly assigned to 3 groups and received either purified water, L-citrulline (500 mg/kg/day), or a combination of L-citrulline (500 mg/kg/day) and GSH (50 mg/kg/day) by oral gavage for 3 days. Blood samples were collected and plasma NOx (nitrite + nitrate) assessed. In phase three, resistance-trained males were randomly assigned to orally ingest either cellulose placebo (2.52 g/day), L-citrulline (2 g/day), GSH (1 g/day), or L-citrulline (2 g/day) + GSH (200 mg/day) for 7 days, and then perform a resistance exercise session involving 3 sets of 10-RM involving the elbow flexors.
    [Show full text]
  • The Responses of Glutathione and Antioxidant Enzymes to Hyperoxia in Developing Lung
    LUNG GLUTATHIONE RESPONSE TO HYPEROXIA 8 19 Physiol 55: 1849- 1853 alkalosis on cerebral blood flow in cats. Stroke 5:324-329 21. Lou HC, Lassen NA. Fnis-Hansen B 1978 Decreased cerebral blood flow after 24. Arvidsson S, Haggendal E, Winso 1 1981 Influence on cerebral blood flow of administration of sodium bicarbonate in the distressed newborn infant. Acta infusions of sodium bicarbonate during respiratory acidosis and alkalosis in Neurol Scand 57:239-247 the dog. Acta Anesthesiol Scand 25:146-I52 22. Rapoport SI 1970 Effect ofconcentrated solutions on blood-brain barrier. Am 25. Pannier JL, Weyne J, Demeester G, Leusen 1 1978 Effects of non-respiratory J Physiol 219270-274 alkalosis on brain tissue and cerebral blood flow in rats with damaged blood- 23. Pannier JL, Demeester MS, Leuscn 1 1974 Thc influence of nonrcspiratory brain hamer. Stroke 9:354-359 003 1-3998/85/1908-08 19$0:.00/0 PEDIATRIC RESEARCH Vol. 19, No. 8, 1985 Copyright 8 1985 International Pediatric Research Foundation, Inc Prinled in U.S.A. The Responses of Glutathione and Antioxidant Enzymes to Hyperoxia in Developing Lung JOSEPH B. WARSHAW, CHARLIE W. WILSON, 111, KOTARO SAITO, AND RUSSELL A. PROUGH Departmmls qfP~diufricsarid Biochemistr,~, The University of Texas Health Srience Center ul DaNas. Dallas, Texas 75235 ABSTRACT. Total glutathione levels and the activity of Abbreviations enzymes associated with antioxidant protection in neonatal lung are increased in response to hyperoxia. GIutathione SOD, superoxide dismutiase levels in developing rat lung decreased from 24 nmol/mg GSH, reduced glutathione protein on day 19 of gestation to approximately 12 nmol/ GSSG, oxidized glutathione mg protein at birth.
    [Show full text]
  • Serum Metabolite Profiles As Potential Biochemical Markers in Young
    www.nature.com/scientificreports OPEN Serum metabolite profles as potential biochemical markers in young adults with community- acquired pneumonia cured by moxifoxacin therapy Bo Zhou1, Bowen Lou2,4, Junhui Liu3* & Jianqing She2,4* Despite the utilization of various biochemical markers and probability calculation algorithms based on clinical studies of community-acquired pneumonia (CAP), more specifc and practical biochemical markers remain to be found for improved diagnosis and prognosis. In this study, we aimed to detect the alteration of metabolite profles, explore the correlation between serum metabolites and infammatory markers, and seek potential biomarkers for young adults with CAP. 13 Eligible young mild CAP patients between the ages of 18 and 30 years old with CURB65 = 0 admitted to the respiratory medical department were enrolled, along with 36 healthy participants as control. Untargeted metabolomics profling was performed and metabolites including alcohols, amino acids, carbohydrates, fatty acids, etc. were detected. A total of 227 serum metabolites were detected. L-Alanine, 2-Hydroxybutyric acid, Methylcysteine, L-Phenylalanine, Aminoadipic acid, L-Tryptophan, Rhamnose, Palmitoleic acid, Decanoylcarnitine, 2-Hydroxy-3-methylbutyric acid and Oxoglutaric acid were found to be signifcantly altered, which were enriched mainly in propanoate and tryptophan metabolism, as well as antibiotic-associated pathways. Aminoadipic acid was found to be signifcantly correlated with CRP levels and 2-Hydroxy-3-methylbutyric acid and Palmitoleic acid with PCT levels. The top 3 metabolites of diagnostic values are 2-Hydroxybutyric acid(AUC = 0.90), Methylcysteine(AUC = 0.85), and L-Alanine(AUC = 0.84). The AUC for CRP and PCT are 0.93 and 0.91 respectively.
    [Show full text]
  • Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes
    antioxidants Review Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes Gethin J. McBean School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland; [email protected]; Tel.: +353-1-716-6770 Received: 13 July 2017; Accepted: 1 August 2017; Published: 3 August 2017 Abstract: This review discusses the current understanding of cysteine and glutathione redox balance in astrocytes. Particular emphasis is placed on the impact of oxidative stress and astrocyte activation on pathways that provide cysteine as a precursor for glutathione. The effect of the disruption of thiol-containing amino acid metabolism on the antioxidant capacity of astrocytes is also discussed. − Keywords: cysteine; cystine; cysteamine; cystathionine; glutathione; xc cystine-glutamate exchanger; transsulfuration 1. Introduction Thiol groups, whether contained within small molecules, peptides, or proteins, are highly reactive and prone to spontaneous oxidation. Free cysteine readily oxidises to its corresponding disulfide, cystine, that together form the cysteine/cystine redox couple. Similarly, the tripeptide glutathione (γ-glutamyl-cysteinyl-glycine) exists in both reduced (GSH) and oxidised (glutathione disulfide; GSSG) forms, depending on the oxidation state of the sulfur atom on the cysteine residue. In the case of proteins, the free sulfhydryl group on cysteines can adopt a number of oxidation states, ranging from disulfides (–S–S–) and sulfenic acids (–SOOH), which are reversible, to the more oxidised sulfinic (–SOO2H) and sulfonic acids (–SOO3H), which are not. These latter species may arise as a result of chronic and/or severe oxidative stress, and generally indicate a loss of function of irreversibly oxidised proteins. Methionine residues oxidise to the corresponding sulfoxide, which can be rescued enzymatically by methionine sulfoxide reductase [1].
    [Show full text]
  • Glutathione Precursors DIETARY SUPPLEMENT
    Glutathione Precursors DIETARY SUPPLEMENT Supports formation of the key antioxidant compound glutathione • Enhances free radical scavenging* • Provides the three precursors needed to form glutathione within the body: N-acetyl-L-cysteine (NAC), glutamic acid and glycine* • Includes α-lipoic acid Supplement Facts Serving Size 1 Capsule/ Servings per Container 30 GENESTRA BRANDS Glutathione Precursors helps to protect against oxidative Each Capsule Contains N-acetyl-L-cysteine (NAC) 200 mg* stress and supports glutathione formation. Glutathione, or γ-glutamyl- L-glutamic acid 200 mg* cysteinylglycine (GSH), is the primary intracellular antioxidant involved in DL-alpha lipoic acid 200 mg* preventing lipid and protein oxidation, and is a critical component in the L-glycine 100 mg* 1,2 enzymatic process used to detoxify hydroxide peroxide (H2O2). Cysteine, * Daily Value not established glutamic acid and glycine are the three essential precursors for endogenous Other ingredients: Hypromellose, magnesium stearate glutathione production.3 Supplementation with NAC, cysteine, and glycine has Recommended Adult Dose: Take one capsule daily with a 4-6 been shown to increase GSH levels. meal or as recommended by your healthcare practitioner. Product Size: 30 Vegetable Capsules Product Code: 10366 Scientific Rationale: GSH is considered an important free radical scavenger. In addition to its levels synthesis rates comparable to measurements obtained from a younger antioxidant effects, it also plays a key role in amino acid transport across adult control group. Participants received 0.81 mmol cysteine/kg/day (as membranes, gene regulation, and protein synthesis and degradation.7 GSH n-acetylcysteine) and 1.33 mmol glycine/kg/day for 2 weeks. At baseline synthesis occurs primarily in the liver, following hepatic uptake of its precursors and following supplementation, blood samples were obtained and analyzed cysteine, glutamic acid and glycine.
    [Show full text]
  • L-Proline Activates Mammalian Target of Rapamycin Complex 1 and Modulates Redox Environment in Porcine Trophectoderm Cells
    biomolecules Article L-Proline Activates Mammalian Target of Rapamycin Complex 1 and Modulates Redox Environment in Porcine Trophectoderm Cells Ning Liu 1,2, Ying Yang 1, Xuemeng Si 1, Hai Jia 1, Yunchang Zhang 1, Da Jiang 1, Zhaolai Dai 1 and Zhenlong Wu 1,2,* 1 State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing 100193, China; [email protected] (N.L.); [email protected] (Y.Y.); [email protected] (X.S.); [email protected] (H.J.); [email protected] (Y.Z.); [email protected] (D.J.); [email protected] (Z.D.) 2 Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China * Correspondence: [email protected]; Tel.: +86-10-6273-1003 Abstract: L-proline (proline) is a key regulator of embryogenesis, placental development, and fetal growth. However, the underlying mechanisms that support the beneficial effects of proline are largely unknown. This study used porcine trophectoderm cell line 2 (pTr2) to investigate the underlying mechanisms of proline in cell proliferation and redox homeostasis. Cells were cultured in the presence of 0, 0.25, 0.50, or 1.0 mmol/L proline for an indicated time. The results showed that 0.5 and 1.0 mmol/L proline enhanced cell viability. These effects of proline (0.5 mmol/L) were accompanied by the enhanced protein abundance of p-mTORC1, p-p70S6K, p-S6, and p-4E-BP1. Additionally, Citation: Liu, N.; Yang, Y.; Si, X.; Jia, proline dose-dependently enhanced the mRNA expression of proline transporters [solute carrier H.; Zhang, Y.; Jiang, D.; Dai, Z.; Wu, Z.
    [Show full text]