The role of iron overload on oxidative stress in sickle cell anemia

Santos, Talyta Ellen de Jesus dos; Sousa, Geane Felix de; Barbosa, Maritza Cavalcante; Gonçalves, Raquel

doi:10.2217/bmm.12.71

Cited by 9 publications

(8 citation statements)

References 22 publications

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“…Iron overload is biochemically harmful, resulting in tissue damage through the conversion of H 2 O 2 to free radical ions that attack cellular membrane lipids, proteins, and DNA. 45 The results of the present study show that patients with SCA have significantly higher serum iron levels than individuals with normal Hb. The positive correlation between the serum iron and MDA levels in patients with SCA reflects the role of iron in lipid peroxidation.…”

Section: Discussionsupporting

confidence: 50%

“…In addition, the significant positive correlation between the serum ferritin and MDA levels may indicate that iron overload plays a role in oxidative stress, because a high level of the oxidation product MDA was associated with low levels of antioxidant enzymes and their cofactors. Although Dos Santos et al, found a similar correlation; 45 another study of patients with SCA who received transfusion did not observe this correlation. 46 Studies of older patients, 47 and patients who had received blood transfusion, 46 found that patients with SCA had higher serum copper and iron levels and lower serum zinc levels than individuals with normal Hb.…”

Section: Discussionmentioning

confidence: 84%

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Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia

Al-Naama

Hassan

Mehdi³

2015

Qatar Medical Journal

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Background: Sickle cell anemia (SCA) is an inherited blood disease with known complications as a result of certain pathophysiological dysfunctions. It has been suggested that an increase in oxidative stress contributes to the incidence of these changes. Objectives: This study investigated the oxidant/antioxidant status of patients with SCA, and evaluated the effect of SCA on antioxidant enzymes and their cofactors. Methods: The study included 42 patients with SCA (in steady state), and a control group of 50 age-matched individuals without SCA. Serum malondialdehyde (MDA), copper, zinc, ferritin and iron levels, red blood cell (RBC) superoxide dismutase (SOD) and catalase levels were measured for the SCA and control groups. Results: Significantly lower levels of antioxidant enzymes (RBC SOD and catalase) and higher serum MDA levels (biomarker of oxidative stress) were found in SCA patients compared to the control group (all p < 0.001). Increased levels of serum ferritin, iron and copper and decreased zinc concentrations were also found in the SCA patients compared to the control group (all p < 0.001). In the SCA group, there were significant negative correlations between MDA levels and RBC SOD, RBC catalase, and serum zinc levels (p < 0.01), while a significant positive correlation between MDA with serum copper and iron levels (p < 0.01) was observed. Conclusion: SCA is associated with alterations in markers of oxidative stress including an increased MDA level, decreased antioxidant enzyme levels, and altered levels of enzyme cofactors (zinc, copper, and iron). This suggests that these antioxidant enzymes could be used as effective therapeutic targets for the treatment of this disease and supplementation of patients with substances with antioxidant properties may reduce the complications of this disease.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 84%

Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia

Al-Naama

Hassan

Mehdi³

2015

Qatar Medical Journal

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“…mTOR pathways are essential to cell growth and proliferation, and mTOR inhibition may therefore suppress bone marrow erythropoiesis (Aliyu et al , ) , (Dos Santos et al , ). To study erythropoiesis in our SCD (BMT) mice, bone marrow cells were isolated and analysed for haematopoietic progenitor cells using flow cytometry following 1 week of treatment.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to supportive treatment for acute complications, current therapies for SCD include blood transfusions (DeBaun et al, 2014) and treatment with hydroxycarbamide (also termed hydroxyurea; Lanzkron et al, 2008). Repeated blood transfusions have been shown to reduce the risk of recurrent stroke although iron overload with haemochromatosis is a long-term complication (Aliyu et al, 2006;Dos Santos et al, 2012). Prolonged treatment with hydroxycarbamide also appears to be beneficial in preventing some SCD complications (Lanzkron et al, 2008).…”

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confidence: 99%

mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease

et al. 2016

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Summary Mechanistic target of rapamycin (mTOR) has been shown to play an important role in red blood cell physiology, with inhibition of mTOR signalling leading to alterations in erythropoiesis. To determine if mTOR inhibition would improve anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual mTORC1/2 inhibitor, INK128. 1 week after daily oral drug treatment, erythrocyte count, haemoglobin, and haematocrit were all significantly increased while reticulocyte counts were reduced. These parameters remained stable during 3 weeks of treatment. Similar effects were observed following oral treatment with the mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle cell erythrocytes in circulation, reduced spleen size, and reduced renal and hepatic iron accumulation in SCD mice. Following middle cerebral artery occlusion, stroke size was reduced in SCD mice treated with sirolimus. In conclusion, mTOR inhibition is protective against anaemia and organ damage in a murine model of SCD.

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“…Despite iron chelation therapy, chronic transfusion therapy often leads to massive iron overload in liver, heart, brain, and endocrine organs and subsequent organ dysfunction that ultimately results in death [ 3 , 6 , 7 ]. Iron overload may also occur in patients who do not receive multiple blood transfusions due to the absorption from the gut [ 8 ]. Oxidative stress, inflammation, hepatic involvements, osteoporosis, and cardiac and renal insufficiency are major causes of iron overload related morbidity in patients with β -TM [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Effects of Silymarin and Its Flavonolignan Components in Patients withβ-Thalassemia Major: A Comprehensive Review in 2015

Darvishi‐Khezri

Salehifar

Kosaryan

et al. 2016

Advances in Pharmacological Sciences

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Major β-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of β-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with β-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.

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The role of iron overload on oxidative stress in sickle cell anemia

Abstract: The results demonstrated that IO is an important risk factor for enhanced oxidative stress in SCA.

Cited by 9 publications

References 22 publications

Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia

Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia

mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease

Potential Effects of Silymarin and Its Flavonolignan Components in Patients withβ-Thalassemia Major: A Comprehensive Review in 2015

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