Erythrocyte and plasma oxidative stress appears to be compensated in patients with sickle cell disease during a period of relative health, despite the presence of known oxidative agents

Detterich, Jon; Liu, Honglei; Suriany, Silvie; Kato, Roberta M.; Chalacheva, Patjanaporn; Tedla, Bruke; Shah, Payal; Khoo, Michael C. K.; Wood, John C.; Coates, Thomas D.; Milne, Ginger L.; Oh, Joo–Yeun; Patel, Rakesh P.; Forman, Henry Jay

doi:10.1016/j.freeradbiomed.2019.07.004

Cited by 14 publications

(24 citation statements)

References 55 publications

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“…Although antioxidant enzymes are supposed to be overwhelmed by ROS in a SCA context, we observed higher CAT activity in the plasma of SS children compared to AA controls. These findings support those of Detterich et al who demonstrated that oxidative stress can be (at least partly) compensated within the RBC or plasma of patients at steady-state [ 44 ]. Oxidative stress results from an imbalance between pro-oxidant and antioxidant activities.…”

Section: Discussionsupporting

confidence: 91%

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Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

et al. 2020

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Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs233322) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity.

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Section: Discussionsupporting

confidence: 91%

“…Many studies previously investigated oxidative stress markers in SCD populations partially HU-treated [ 7 , 12 , 44 , 53 ]. However, their conclusions could be challenged since HU treatment has been shown to modulate oxidative stress [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

et al. 2020

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“…These patients are at remarkably high risk of severe vascular disease if not on transfusion therapy, and they are at risk for iron overload if they remain on transfusion therapy. This is problematic at the time of transition and when determining continuation of transfusion therapy vs transition to hydroxyurea treatment, 48 initiation of exchange transfusion therapy that may stabilize cell free hemoglobin 49 and improve TRV 50 or consideration of curative therapies. Patients can be cured by marrow transplant and gene therapies are on the horizon.…”

Section: Discussionmentioning

confidence: 99%

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups ‐ revisiting this controversial concept after 16 years of additional evidence

et al. 2020

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Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi‐level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S′) and diastole (E′), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty‐eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional‐hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end‐organ failure. On Cox proportional‐hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S′ results in a 91% increase, and 1 cm/s decrease in E′ results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.

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“…Advanced lipoxidation end-products (ALEs) (adducts with oxylipin carbonyl compounds) F2-isoprostanes adducts Biomarker of lipid peroxidation Plasma [119][120][121]…”

Section: Specificity In Scd Tissue Referencesmentioning

confidence: 99%

Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy

et al. 2021

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Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb), which affects approximately a million people worldwide. It is characterized by a single nucleotide substitution in the β-globin gene, leading to the production of abnormal sickle hemoglobin (HbS) with multi-system consequences. HbS polymerization is the primary event in SCD. Repeated polymerization and depolymerization of Hb causes oxidative stress that plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e., by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

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Erythrocyte and plasma oxidative stress appears to be compensated in patients with sickle cell disease during a period of relative health, despite the presence of known oxidative agents

Cited by 14 publications

References 55 publications

Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups ‐ revisiting this controversial concept after 16 years of additional evidence

Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy

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