Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity

Background: The oxidation of the methionine adenosyltransferase (MAT) by the combined impact of peroxides contaminating parenteral nutrition (PN) and oxidized redox potential of glutathione is suspected to explain its inhibition observed in animals. A modification of MAT activity is suspected to be...

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Main Authors: Wesam Elremaly, Ibrahim Mohamed, Thérèse Rouleau, Jean-Claude Lavoie
Format: Article
Language:English
Published: Elsevier 2016-08-01
Series:Redox Biology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231715300185
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author Wesam Elremaly
Ibrahim Mohamed
Thérèse Rouleau
Jean-Claude Lavoie
author_facet Wesam Elremaly
Ibrahim Mohamed
Thérèse Rouleau
Jean-Claude Lavoie
author_sort Wesam Elremaly
collection DOAJ
description Background: The oxidation of the methionine adenosyltransferase (MAT) by the combined impact of peroxides contaminating parenteral nutrition (PN) and oxidized redox potential of glutathione is suspected to explain its inhibition observed in animals. A modification of MAT activity is suspected to be at origin of the PN-associated liver disease as observed in newborns. We hypothesized that the correction of redox potential of glutathione by adding glutathione in PN protects the MAT activity. Aim: To investigate whether the addition of glutathione to PN can reverse the inhibition of MAT observed in animal on PN. Methods: Three days old guinea pigs received through a jugular vein catheter 2 series of solutions. First with methionine supplement, (1) Sham (no infusion); (2) PN: amino acids, dextrose, lipids and vitamins; (3) PN-GSSG: PN+10 μM GSSG. Second without methionine, (4) D: dextrose; (5) D+180 μM ascorbylperoxide; (6) D+350 μM H2O2. Four days later, liver was sampled for determination of redox potential of glutathione and MAT activity in the presence or absence of 1 mM DTT. Data were compared by ANOVA, p<0.05. Results: MAT activity was 45±4% lower in animal infused with PN and 23±7% with peroxides generated in PN. The inhibition by peroxides was associated with oxidized redox potential and was reversible by DTT. Correction of redox potential (PN+GSSG) or DTT was without effect on the inhibition of MAT by PN. The slope of the linear relation between MAT activity and redox potential was two fold lower in animal infused with PN than in others groups. Conclusion: The present study suggests that prevention of peroxide generation in PN and/or correction of the redox potential by adding glutathione in PN are not sufficient, at least in newborn guinea pigs, to restore normal MAT activity.
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spelling doaj.art-3d3834ceaf004707ac19dcfcbad08af62022-12-21T18:40:17ZengElsevierRedox Biology2213-23172016-08-018C182310.1016/j.redox.2015.12.003Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activityWesam Elremaly0Ibrahim Mohamed1Thérèse Rouleau2Jean-Claude Lavoie3Department of Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5Department of Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5Department of Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5Background: The oxidation of the methionine adenosyltransferase (MAT) by the combined impact of peroxides contaminating parenteral nutrition (PN) and oxidized redox potential of glutathione is suspected to explain its inhibition observed in animals. A modification of MAT activity is suspected to be at origin of the PN-associated liver disease as observed in newborns. We hypothesized that the correction of redox potential of glutathione by adding glutathione in PN protects the MAT activity. Aim: To investigate whether the addition of glutathione to PN can reverse the inhibition of MAT observed in animal on PN. Methods: Three days old guinea pigs received through a jugular vein catheter 2 series of solutions. First with methionine supplement, (1) Sham (no infusion); (2) PN: amino acids, dextrose, lipids and vitamins; (3) PN-GSSG: PN+10 μM GSSG. Second without methionine, (4) D: dextrose; (5) D+180 μM ascorbylperoxide; (6) D+350 μM H2O2. Four days later, liver was sampled for determination of redox potential of glutathione and MAT activity in the presence or absence of 1 mM DTT. Data were compared by ANOVA, p<0.05. Results: MAT activity was 45±4% lower in animal infused with PN and 23±7% with peroxides generated in PN. The inhibition by peroxides was associated with oxidized redox potential and was reversible by DTT. Correction of redox potential (PN+GSSG) or DTT was without effect on the inhibition of MAT by PN. The slope of the linear relation between MAT activity and redox potential was two fold lower in animal infused with PN than in others groups. Conclusion: The present study suggests that prevention of peroxide generation in PN and/or correction of the redox potential by adding glutathione in PN are not sufficient, at least in newborn guinea pigs, to restore normal MAT activity.http://www.sciencedirect.com/science/article/pii/S2213231715300185Parenteral nutritionPeroxideNewbornMethionine adenosyltransferaseThiol oxidationRedox potential of glutathione.
spellingShingle Wesam Elremaly
Ibrahim Mohamed
Thérèse Rouleau
Jean-Claude Lavoie
Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
Redox Biology
Parenteral nutrition
Peroxide
Newborn
Methionine adenosyltransferase
Thiol oxidation
Redox potential of glutathione.
title Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
title_full Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
title_fullStr Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
title_full_unstemmed Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
title_short Impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
title_sort impact of glutathione supplementation of parenteral nutrition on hepatic methionine adenosyltransferase activity
topic Parenteral nutrition
Peroxide
Newborn
Methionine adenosyltransferase
Thiol oxidation
Redox potential of glutathione.
url http://www.sciencedirect.com/science/article/pii/S2213231715300185
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