Oxidative alterations in sickle cell disease: Possible involvement in disease pathogenesis

Öztaş, Yeşim; Yalçınkaya, Ahmet

doi:10.5315/wjh.v6.i3.55

Cited by 9 publications

(12 citation statements)

References 80 publications

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“…36 Consequently, ischemia-reperfusion injury may worsen oxidative stress by the generation of more ROS. 20 Furthermore, our findings revealed that glutathione peroxidase, a symbolic antioxidant enzyme, was considerably reduced in HbSS, HbSC, and HbAC groups against the normal group. This observation was consistent with some previous studies.…”

Section: Discusionmentioning

confidence: 61%

“…The study shows that a number of factors may be culprit of free radical induced oxidative damage in Hb variants, with and without iron effects . Excluding iron effects, vaso‐occlusion induced ischemia‐reperfusion injury is a notable inducer of xanthine oxidase, NADPH oxidase, and nitric oxide synthase enzymes, which may trigger many oxidative events and ultimately damage erythrocytes, especially in SCDs.…”

Section: Discusionmentioning

confidence: 96%

“…Similarly, we observed reductions in red blood cells (RBCs) indicated by low hematocrit levels as well as in the Hb concentrations, among the SCD patients and Hb S traits (HbAS) (Figure ). Report indicates that the reduced number of RBCs and Hb levels may trigger lower partial pressure of oxygen, while partially oxygenated Hb prompts autooxidation of Hb, thus converting to methemoglobin with resultant production of reactive superoxide ions . In this process, the evolved superoxide ion is fast converted to hydrogen peroxide (H 2 O 2 ) accumulating free radicals, which are detrimental to the erythrocyte membrane and induction of lipid radicals, aldehydes, and other reactive products …”

Section: Discusionmentioning

confidence: 99%

“…Excluding iron effects, vaso‐occlusion induced ischemia‐reperfusion injury is a notable inducer of xanthine oxidase, NADPH oxidase, and nitric oxide synthase enzymes, which may trigger many oxidative events and ultimately damage erythrocytes, especially in SCDs. Besides, irregularities in the architecture of erythrocyte membrane proteins of Hb variants and chronic inflammation (in SCDs) are other plausible factors . In addition, reduced antioxidant capacity has been linked with the reduced serum iron level that may in turn affect the production of iron‐containing proteins, particularly antioxidant enzymes such as catalase (CAT) and peroxidase levels .…”

Section: Discusionmentioning

confidence: 99%

“…Report indicates that the reduced number of RBCs and Hb levels may trigger lower partial pressure of oxygen, while partially oxygenated Hb prompts autooxidation of Hb, thus converting to methemoglobin with resultant production of reactive superoxide ions. 20,21 In this process, the evolved superoxide ion is fast converted to hydrogen peroxide (H 2 O 2 ) accumulating free radicals, which are detrimental to the erythrocyte membrane and induction of lipid radicals, aldehydes, and other reactive products. 21 The current study also showed elevation of malondialdehyde (MDA) in blood levels of all common Hb variants when evaluated against the controls.…”

Section: Discusionmentioning

confidence: 99%

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Assessment of iron status and interplay between lipid peroxidation and antioxidant capacity in common hemoglobin variants in Osun State, southwestern Nigeria

Ajibola

Adedokun

Oduola

et al. 2019

The Kaohsiung J of Med Scie

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INTRODUCTION Hemoglobin (Hb) and iron are prooxidants in nature and sources of free radicals in the biological system of all Hb phenotypes. Recent evidence linked abnormal hemoglobin S and C (HbSC) in sickle cell disease (SCD) to various complications in multiple oxidative processes. However, similar studies in relation to abnormal Hb traits are sparse. Besides, reports on activities of antioxidant enzymes and iron status in SCDs are still contradictory. This study assessed the interplay between lipid peroxidation and antioxidant defense capacity in various Hb variants. We enrolled 193 participants with different Hb phenotypes. They were consecutive patients with sickle cell anemia (HbSS, n = 32) and hemoglobin SC (HbSC) disease (n = 28) regularly followed up in a steady state. Other participants were subjects with abnormal Hb traits (HbAS, n = 50; HbAC, n = 33) and normal controls (HbAA, n = 50). The hematocrit (Hct) level, hemoglobin (Hb) concentration, iron status, and biochemical parameters including malondialdehyde (MDA), total antioxidant status (TAS), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes were investigated simultaneously. The MDA and SOD levels were significantly higher (P < 0.05) in Hb variants in order of HbSS>HbSC>HbAC>HbAS when compared with controls. Conversely, GPx and TAS levels showed significant reductions (P < 0.05). Similarly, Hct, Hb, and iron concentrations showed significant reductions (P < 0.05) sequentially following HbAC > HbAS > HbSC > HbSS compared with controls. The results suggest that both SCDs and the carriers were relatively more vulnerable to systemic oxidative stress against normal phenotype, and may be owing to ineffective antioxidant mechanisms needed for keeping spontaneous generations of free radicals in control without necessarily iron‐mediated.

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Section: Discusionmentioning

confidence: 61%

Section: Discusionmentioning

confidence: 96%

Section: Discusionmentioning

confidence: 99%

Section: Discusionmentioning

confidence: 99%

Section: Discusionmentioning

confidence: 99%

See 3 more Smart Citations

Assessment of iron status and interplay between lipid peroxidation and antioxidant capacity in common hemoglobin variants in Osun State, southwestern Nigeria

Ajibola

Adedokun

Oduola

et al. 2019

The Kaohsiung J of Med Scie

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Sickling-preventive effects of rutin is associated with modulation of deoxygenated haemoglobin, 2,3-bisphosphoglycerate mutase, redox status and alteration of functional chemistry in sickle erythrocytes

Muhammad

Waziri

Forcados

et al. 2019

Heliyon

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Sickle cell anaemia is a hereditary disease branded by an upsurge in generation of ROS, irregular iron release and little or no antioxidant activity which can lead to cellular injuries due to oxidative stress resulting in severe symptoms including anaemia and pain. The disease is caused by a mutated version of the gene that helps make haemoglobin, the protein that carries oxygen in red blood cells. We used in silico and in vitro experiments to examine the antisickling effects of rutin for the first time by means of before and after induction approaches in sickle erythrocytes. Rutin was docked against deoxy-haemoglobin and 2,3-bisphosphoglycerate mutase, revealing binding energies (-27.329 and -25.614 kcal/mol) and K i of 0.989μM and 0.990 μM at their catalytic sites through strong hydrophobic and hydrogen bond interactions. Sickling was thereafter, induced at 3 h with 2% metabisulphite. Rutin prevented sickling maximally at 12.3μM and reversed same at 16.4μM, by 78.5% and 69.9%, one-to-one. Treatment with rutin significantly (P < 0.05) reinvented the integrity of erythrocytes membrane as evident from the practical % haemolysis compared to induced erythrocytes. Rutin also significantly (P < 0.05) prevented and reversed lipid peroxidation relative to untreated. Likewise, GSH, CAT levels were observed to significantly (P < 0.05) increase with concomitant significant (P < 0.05) decrease in SOD activity based on administration of rutin after sickling induction approach. Furthermore, FTIR results showed that treatment with rutin favourably altered the functional chemistry, umpiring from shifts and functional groups observed. It can thus be deduced that, antisickling effects of rutin may be associated with modulation of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, alteration of redox homeostasis and functional chemistry of sickle erythrocytes.

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Understanding the prion-like behavior of mutant p53 proteins in triple-negative breast cancer pathogenesis: The current therapeutic strategies and future directions

Naeimzadeh,

Tajbakhsh,

Fallahi

2024

Heliyon

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Oxidative alterations in sickle cell disease: Possible involvement in disease pathogenesis

Cited by 9 publications

References 80 publications

Assessment of iron status and interplay between lipid peroxidation and antioxidant capacity in common hemoglobin variants in Osun State, southwestern Nigeria

Assessment of iron status and interplay between lipid peroxidation and antioxidant capacity in common hemoglobin variants in Osun State, southwestern Nigeria

Sickling-preventive effects of rutin is associated with modulation of deoxygenated haemoglobin, 2,3-bisphosphoglycerate mutase, redox status and alteration of functional chemistry in sickle erythrocytes

Understanding the prion-like behavior of mutant p53 proteins in triple-negative breast cancer pathogenesis: The current therapeutic strategies and future directions

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