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.
Highlights
Oxidative stress (OS) causes irreversible damage to DNA, lipids, and proteins [1,2,3], and is defined as a disruption of redox signaling and control [4,5,6]
After adjusting for age, gender, and race, children admitted to the pediatric intensive care unit (PICU) had 2.5 times less Cys (2.29 vs. 0.91 μM; p = 0.009), 2.8 times less CySS (2.98 vs. 1.05 μM; p = 0.011), and 2.5 times less Total Cys (8.52 vs. 3.41 μM; p = 0.01) (Figure 1A)
Children admitted to the PICU had no difference in GSH concentrations (0.29 vs. 0.22 μM; p = 0.573) or Total GSH (0.37 vs. 0.69 μM; p = 0.106), but PICU patients had 13 times more GSH and its glutathione disulfide (GSSG) (0.01 vs. 0.13 μM; p < 0.001) than healthy control children (Figure 1B)
Summary
Oxidative stress (OS) causes irreversible damage to DNA, lipids, and proteins [1,2,3], and is defined as a disruption of redox signaling and control [4,5,6]. The thiols cysteine (Cys) and glutathione (GSH) are common sources of reducing equivalents for neutralizing oxidative stress. While other small molecule anti-oxidants such as ascorbic acid, uric acid, tocopherols, and carotenoids are important in maintaining redox state of cells, the relative contribution of low molecular weight thiols to total antioxidant capacity is not clear. The toxicity of Cys is controlled by incorporating cysteine into the tripeptide GSH [13]. While Cys and CySS constitute the predominant lowmolecular-weight thiol-disulfide pool in human plasma [14], GSH is more likely to remain reduced in an oxidative environment than Cys. GSH is maintained in tissues at millimolar concentration with a relatively reduced redox state [15], indicating that the Cys/CySS and GSH/GSSG pool are not in equilibrium [14]. 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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call