Comparison of Glutathione, Cysteine, and Their Redox Potentials in the Plasma of Critically Ill and Healthy Children

Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes. To compare the concentrations of plasma redox m...

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Veröffentlicht in:Frontiers in pediatrics Jg. 3; S. 46
Hauptverfasser: Grunwell, Jocelyn R., Gillespie, Scott E., Ward, Janine M., Fitzpatrick, Anne M., Brown, Lou Ann, Gauthier, Theresa W., Hebbar, Kiran B.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 26.05.2015
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ISSN:2296-2360, 2296-2360
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Abstract Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes. To compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children. We performed a prospective clinical observational study of children ages ≤18 years and weight ≥6 kg, who were hospitalized between January 2010 and April 2012 in a 30-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). We measured the plasma concentrations of Cys, CySS, GSH, and GSSG within the first 24 h of PICU arrival, and we calculated the redox potential for the Cys/CySS (Eh Cys/CySS) and GSH/GSSG (Eh GSH/GSSG) thiol/disulfide pairs in the plasma of 61 critically ill children and 16 healthy control children. Critically ill children have less Cys (p = 0.009), less CySS (p = 0.011), less Total Cys ([Cys] + 2[CySS], p = 0.01), more GSSG (p < 0.001), and more oxidized Eh GSH/GSSG (p < 0.001) compared to healthy children. Our results demonstrate that in the presence of pediatric critical illness, the Total Cys/CySS thiol pool decreases while GSH is likely one component of the cellular redox system that reduces CySS back to Cys, thus maintaining Eh Cys/CySS. The Total Cys pool is more abundant than the Total GSH pool in the plasma of children. Further investigation is needed to elucidate the differences in redox potentials in subgroups of critically ill children, and to determine whether differences in redox metabolite concentrations and redox potentials correlate with severity of critical illness and clinical outcomes.
AbstractList Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes. To compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children. We performed a prospective clinical observational study of children ages ≤18 years and weight ≥6 kg, who were hospitalized between January 2010 and April 2012 in a 30-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). We measured the plasma concentrations of Cys, CySS, GSH, and GSSG within the first 24 h of PICU arrival, and we calculated the redox potential for the Cys/CySS (Eh Cys/CySS) and GSH/GSSG (Eh GSH/GSSG) thiol/disulfide pairs in the plasma of 61 critically ill children and 16 healthy control children. Critically ill children have less Cys (p = 0.009), less CySS (p = 0.011), less Total Cys ([Cys] + 2[CySS], p = 0.01), more GSSG (p < 0.001), and more oxidized Eh GSH/GSSG (p < 0.001) compared to healthy children. Our results demonstrate that in the presence of pediatric critical illness, the Total Cys/CySS thiol pool decreases while GSH is likely one component of the cellular redox system that reduces CySS back to Cys, thus maintaining Eh Cys/CySS. The Total Cys pool is more abundant than the Total GSH pool in the plasma of children. Further investigation is needed to elucidate the differences in redox potentials in subgroups of critically ill children, and to determine whether differences in redox metabolite concentrations and redox potentials correlate with severity of critical illness and clinical outcomes.
Background: Oxidative stress (OS) is known to play a role in critical illness due to an imbalance in reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the body’s ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes.Objective: To compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children.Methods: We performed a prospective clinical observational study of children ages ≤ 18 years and weight ≥ 6 kg who were hospitalized between January 2010 and April 2012 in a 30 bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). We measured the plasma concentrations of Cys, CySS, GSH, and GSSG within the first 24 hours of PICU arrival, and we calculated the redox potential for the Cys/CySS (Eh Cys/CySS) and GSH/GSSG (Eh GSH/GSSG) thiol/disulfide pairs in the plasma of 61 critically ill children and 16 healthy control children.Results: Critically ill children have less Cys (p = 0.009), less CySS (p = 0.011), less Total Cys ([Cys] + 2[CySS], p = 0.01), more GSSG (p < 0.001), and more oxidized Eh GSH/GSSG (p < 0.001) compared to healthy children.Conclusions: Our results demonstrate that in the presence of pediatric critical illness, the Total Cys/CySS thiol pool decreases while GSH is likely one component of the cellular redox system that reduces CySS back to Cys thus maintaining Eh Cys/CySS. The Total Cys pool is more abundant than the Total GSH pool in the plasma of children. Further investigation is needed to elucidate the differences in redox potentials in subgroups of critically ill children, and to determine whether differences in redox metabolite concentrations and redox potentials correlate with severity of critical illness and clinical outcomes.
Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes.BACKGROUNDOxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes.To compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children.OBJECTIVETo compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children.We performed a prospective clinical observational study of children ages ≤18 years and weight ≥6 kg, who were hospitalized between January 2010 and April 2012 in a 30-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). We measured the plasma concentrations of Cys, CySS, GSH, and GSSG within the first 24 h of PICU arrival, and we calculated the redox potential for the Cys/CySS (Eh Cys/CySS) and GSH/GSSG (Eh GSH/GSSG) thiol/disulfide pairs in the plasma of 61 critically ill children and 16 healthy control children.METHODSWe performed a prospective clinical observational study of children ages ≤18 years and weight ≥6 kg, who were hospitalized between January 2010 and April 2012 in a 30-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). We measured the plasma concentrations of Cys, CySS, GSH, and GSSG within the first 24 h of PICU arrival, and we calculated the redox potential for the Cys/CySS (Eh Cys/CySS) and GSH/GSSG (Eh GSH/GSSG) thiol/disulfide pairs in the plasma of 61 critically ill children and 16 healthy control children.Critically ill children have less Cys (p = 0.009), less CySS (p = 0.011), less Total Cys ([Cys] + 2[CySS], p = 0.01), more GSSG (p < 0.001), and more oxidized Eh GSH/GSSG (p < 0.001) compared to healthy children.RESULTSCritically ill children have less Cys (p = 0.009), less CySS (p = 0.011), less Total Cys ([Cys] + 2[CySS], p = 0.01), more GSSG (p < 0.001), and more oxidized Eh GSH/GSSG (p < 0.001) compared to healthy children.Our results demonstrate that in the presence of pediatric critical illness, the Total Cys/CySS thiol pool decreases while GSH is likely one component of the cellular redox system that reduces CySS back to Cys, thus maintaining Eh Cys/CySS. The Total Cys pool is more abundant than the Total GSH pool in the plasma of children. Further investigation is needed to elucidate the differences in redox potentials in subgroups of critically ill children, and to determine whether differences in redox metabolite concentrations and redox potentials correlate with severity of critical illness and clinical outcomes.CONCLUSIONOur results demonstrate that in the presence of pediatric critical illness, the Total Cys/CySS thiol pool decreases while GSH is likely one component of the cellular redox system that reduces CySS back to Cys, thus maintaining Eh Cys/CySS. The Total Cys pool is more abundant than the Total GSH pool in the plasma of children. Further investigation is needed to elucidate the differences in redox potentials in subgroups of critically ill children, and to determine whether differences in redox metabolite concentrations and redox potentials correlate with severity of critical illness and clinical outcomes.
Author Grunwell, Jocelyn R.
Gillespie, Scott E.
Ward, Janine M.
Fitzpatrick, Anne M.
Gauthier, Theresa W.
Brown, Lou Ann
Hebbar, Kiran B.
AuthorAffiliation 1 Division of Pediatric Critical Care Medicine, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine , Atlanta, GA , USA
2 Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine , Atlanta, GA , USA
4 Division of Pulmonology, Allergy & Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine , Atlanta, GA , USA
3 Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine , Atlanta, GA , USA
AuthorAffiliation_xml – name: 1 Division of Pediatric Critical Care Medicine, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine , Atlanta, GA , USA
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– name: 3 Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine , Atlanta, GA , USA
– name: 4 Division of Pulmonology, Allergy & Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine , Atlanta, GA , USA
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Keywords redox potential
critical illness
glutathione
oxidative stress
cysteine
pediatric
Language English
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Reviewed by: Felice Su, Stanford University, USA; Michael Shoykhet, Washington University in St. Louis School of Medicine, USA
Specialty section: This article was submitted to Pediatric Critical Care, a section of the journal Frontiers in Pediatrics
Edited by: Kanwaljeet J. S. Anand, University of Tennessee Health Science Center, USA
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Snippet Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's...
Background: Oxidative stress (OS) is known to play a role in critical illness due to an imbalance in reactive oxygen species (ROS) and reactive nitrogen...
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StartPage 46
SubjectTerms Cysteine
Glutathione
Oxidative Stress
Pediatric critical Illness
Pediatrics
redox potential
Title Comparison of Glutathione, Cysteine, and Their Redox Potentials in the Plasma of Critically Ill and Healthy Children
URI https://www.ncbi.nlm.nih.gov/pubmed/26075191
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https://pubmed.ncbi.nlm.nih.gov/PMC4443718
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