Dataset Information

Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study.

ABSTRACT: It is well known that G6PD-deficient individuals are highly susceptible to oxidative stress. However, the differences in the degree of metabolic alterations among patients during an oxidative crisis have not been extensively studied. In this study, we applied mathematical modeling to assess the metabolic changes in erythrocytes of various G6PD-deficient patients during hydrogen peroxide- (H(2)O(2)-) induced perturbation and predict the kinetic properties that elicit redox imbalance after exposure to an oxidative agent. Simulation results showed a discrepancy in the ability to restore regular metabolite levels and redox homeostasis among patients. Two trends were observed in the response of redox status (GSH/GSSG) to oxidative stress, a mild decrease associated with slow recovery and a drastic decline associated with rapid recovery. The former was concluded to apply to patients with severe clinical symptoms. Low V(max) and high K(mG6P) of G6PD were shown to be kinetic properties that enhance consequent redox imbalance.

SUBMITTER: Shimo H

PROVIDER: S-EPMC3184397 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study.

Shimo Hanae H Nishino Taiko T Tomita Masaru M

Advances in hematology 20110928

It is well known that G6PD-deficient individuals are highly susceptible to oxidative stress. However, the differences in the degree of metabolic alterations among patients during an oxidative crisis have not been extensively studied. In this study, we applied mathematical modeling to assess the metabolic changes in erythrocytes of various G6PD-deficient patients during hydrogen peroxide- (H(2)O(2)-) induced perturbation and predict the kinetic properties that elicit redox imbalance after exposur ...[more]

PMID: 21977034

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Project description:BackgroundThe pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required.MethodsCOVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome.ResultsSignificantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects.ConclusionHerein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.

Dataset Information

Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study.

Publications

Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study.

Similar Datasets

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