Suthat Fucharoen

Mahidol University, Krung Thep, Bangkok, Thailand

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Publications (223)734.13 Total impact

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    ABSTRACT: To evaluate the efficacy of deferiprone (DFP), 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) or green tea extract (GTE) in enhancing expression of hepatic hepcidin1 (Hamp1) mRNA and relieving iron overload in β-globin knockout thalassemic mice.
    Asian Pacific Journal of Tropical Biomedicine 10/2015; DOI:10.1016/j.apjtb.2015.09.007
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    ABSTRACT: Objective: Thalassemia is one of the genetic diseases that cause anemia and ineffective erythropoiesis. Increased levels of several inflammatory cytokines have been reported in β-thalassemia and might contribute to ineffective erythropoiesis. However, the mechanism by which tumor necrosis factor-alpha (TNF-α) is involved in ineffective erythropoiesis in thalassemic patients remains unclear. The objective of this study is to investigate the effect of TNF-α on the erythropoietin (EPO) and erythropoietin receptor (EPOR) expression involved in proliferation of β-thalassemia/Hb E erythroid progenitor cells compared with cells from healthy subjects. Materials and methods: CD34-positive cells were isolated from heparinized blood by using the EasySep®CD34 selection kit. Cells were then cultured with suitable culture medium in various concentrations of EPO for 14 days. The effect of TNF-α on percent cell viability was analyzed by trypan blue staining. In addition, the percentage of apoptosis and levels of EPOR protein were measured by flow cytometry Results: Upon EPO treatment, a higher cell number was observed for erythroid progenitor cells from both healthy participants and β-thalassemia/Hb E patients. However, a reduction of apoptosis was found in EPO-treated cells especially for β-thalassemia/Hb E patients. Interestingly, TNF-α caused higher levels of cell apoptosis and lower levels of EPOR protein in thalassemic erythroid progenitor cells. Conclusion: TNF-α caused a reduction in the level of EPOR protein and EPO-induced erythroid progenitor cell proliferation. It is possible that TNF-α could be involved in the mechanism of ineffective erythropoiesis in β-thalassemia/Hb E patients.
    09/2015; DOI:10.4274/tjh.2014.0079

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    ABSTRACT: To evaluate the effect of iron chelators on iron-related pulmonary pathology and oxidative stress in an animal model of β-thalassemia. Pulmonary iron overload was induced in heterozygous β-globin knockout mice (muβth-3/+, BKO). Over a period of 2 weeks, 180 mg of iron/mouse was loaded by intraperitoneal injection of iron dextran, and subsequently treated daily via intraperitoneal with either deferoxamine (DF) or deferiprone (L1) at an equimolar concentration of iron binding (0.2 and 0.6 μmol/g body weight, respectively) for 7 days. Iron loading resulted in iron deposition in peribronchial regions, septa and also in alveolar macrophages with a grading score of 3. This iron burden resulted in lung epithelial injuries, fibrosis and corresponded with increased lipid peroxidation and decreased tissue catalase activity. Treatment with DF or L1 resulted in a reduction of iron-laden alveolar macrophages and decreased oxidative stress and tissue damage, showing the iron mobilizing ability of both compounds. Iron chelation therapy, with DF and L1, may protect against pulmonary damage by sequestering catalytic iron and improving oxidative status. It may be beneficial in the prevention of pulmonary complications in thalassemia. © 2015 S. Karger AG, Basel.
    Pharmacology 08/2015; 96(3-4):192-199. DOI:10.1159/000438994 · 1.67 Impact Factor
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    ABSTRACT: Iron overload cardiomyopathy is the major cause of death in transfusion-dependent thalassemia (TDT) patients. Growing evidence demonstrates that combined iron chelators, or the combination of an iron chelator with antioxidant(s) are effective in diminishing myocardial iron deposition and attenuating cardiac dysfunction. This review comprehensively summarizes basic and clinical reports on the therapeutic efficacy of combined iron chelators, or the combination of an iron chelator with antioxidant(s) on the heart. Promising benefits of these treatments in preventing cardiac dysfunction due to iron overload could provide extensive insight into future therapeutic strategies for better treatment and prevention of cardiomyopathy in TDT patients. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 08/2015; 765:EJP42051. DOI:10.1016/j.ejphar.2015.08.017 · 2.53 Impact Factor
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    Haematologica 06/2015; 100(10). DOI:10.3324/haematol.2015.127373 · 5.81 Impact Factor
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    ABSTRACT: Studies on the antioxidant treatment for thalassemia have reported variable outcomes. However, treatment of thalassemia with a combination of hydrophobic and hydrophilic antioxidants and an iron chelator has not been studied. This study investigated the effects of antioxidant cocktails for the treatment of β-thalassemia/hemoglobin E (HbE), which is the most common form of β-thalassemia in Southeast Asia. Sixty patients were divided into two groups receiving N-acetylcysteine, deferiprone, and either curcuminoids (CUR) or vitamin E (Vit-E), and their hematological parameters, iron load, oxidative stress, and blood coagulation potential were evaluated. Patients were classified as responders if they showed the improvements of the markers of iron load and oxidative stress, otherwise as nonresponders. During treatment, the responders in both groups had significantly decreased iron load, oxidative stress, and coagulation potential and significantly increased antioxidant capacity and hemoglobin concentration. The significantly maximum increase in hemoglobin concentration was 11% at month 4 in CUR group responders and 10% at month 10 in Vit-E group responders. In conclusion, the two antioxidant cocktails can improve anemia, iron overload, oxidative stress, and hypercoagulable state in β-thalassemia/HbE.
    Oxidative medicine and cellular longevity 06/2015; 2015:1-8. DOI:10.1155/2015/537954 · 3.36 Impact Factor
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    Paolo Ricchi · Aldo Filosa · Aurelio Maggio · Suthat Fucharoen ·

    05/2015; 2015:1-2. DOI:10.1155/2015/161434
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  • Journal of the American College of Cardiology 03/2015; 65(10):A901. DOI:10.1016/S0735-1097(15)60901-9 · 16.50 Impact Factor
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    ABSTRACT: Objectives Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are iron chelators currently in clinical use for the treatment of iron overload. Due to difficulties with administration and associated side effects with these three molecules, the search continues for an efficient nontoxic orally active iron chelator. This communication describes the properties of one such candidate, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1).Methods Physicochemical characterisation techniques, including partition coefficient, pKa values and logK values for iron(III). Iron scavenging assays, from iron citrate, nontransferrin bound iron and iron-loaded rats. Cytotoxicity studies using white cells, hepatocytes and cardiomyocytes.Key findingsCM1 possesses high affinity and selectivity for iron(III) and a suitable partition coefficient to permeate membranes. CM1 forms a neutral 3 : 1 iron(III) complex under physiological conditions and so, it is predicted to be capable of entry into mammalian cells to scavenge excess intracellular iron and to efflux from cells as the neutral 3 : 1 complex. CM1 is demonstrated to be orally active and to possess a higher efficacy than DFP in rats. CM1 displays no toxicity to a range of cell types.Conclusion The above promising studies will be extended to monitor the pharmacokinetics and metabolism of CM1. CM1 is an excellent candidate for phase 1 clinical trials.
    02/2015; 67(5). DOI:10.1111/jphp.12373
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    ABSTRACT: Decreased hemoglobinization of red cells resulting in hypochromia and microcytosis are the main features of thalassemia syndromes, and also of iron deficiency anemia (IDA). A simple and reliable method is required to distinguish the two conditions in the routine laboratories. In this study we analyzed the red cell and reticulocyte parameters from 414 samples of various types of thalassemias and IDA and discovered a variety of discriminating criteria including a discrimination index (DI) which should be useful for differential diagnosis.
    Blood Cells Molecules and Diseases 01/2015; 54(4). DOI:10.1016/j.bcmd.2015.01.010 · 2.65 Impact Factor
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    ABSTRACT: β-Thalassemia/HbE disease is caused by a defective β-globin synthesis that leads to accumulation of excess unbound α-globins, and consequently oxidative stress, ineffective erythropoiesis and chronic anemia. Cell replication and oxidative stress are factors contributing to erosion of telomeres responsible for maintaining genomic stability and cell replication capability. In this study, the rate of telomere shortening in β-thalassemia/HbE patients was compared to the rate of telomere shortening in normal individuals. Telomere length was determined from peripheral blood mononuclear cells of 43 β-thalassemia/HbE patients and 22 normal controls using Flow-FISH analysis. The telomere length was shown to be age-dependent in normal group (rs = 0.715, P = 0.002), whereas severity-dependent telomere shortening was observed in the patients. The telomere length of patients who had severe clinical symptoms (10.07 ± 2.15%) was shorter than that of patients who showed mild symptoms (15.59 ± 2.27%), moderate symptoms (14.50 ± 1.41%) and those in the normal group (14.75 ± 3.11%, P < 0.05). Additionally, reticulocyte count and oxidative stress were correlated with telomere length. This indicates that increased oxidative stress and markedly enhanced erythropoiesis in β-thalassemia/HbE patients leads to accelerated telomere erosion in clinically severe patients.
    Blood Cells Molecules and Diseases 01/2015; 55(2). DOI:10.1016/j.bcmd.2015.01.003 · 2.65 Impact Factor
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    ABSTRACT: Furin is a proprotein convertase enzyme. In the liver, it cleaves prohepcidin to form active hepcidin-25, which regulates systemic iron homeostasis. Hepcidin deficiency is a component of several iron overload disorders, including β-thalassemia. Several studies have identified factors that repress hepcidin gene transcription in iron overload. However, the effect of iron overload on furin, a post-translational regulator of hepcidin, has never been evaluated. The present study aimed to investigate the changes in furin and related factors in parenteral iron-overloaded mice, including those with β-thalassemia. Wild-type (WT) and β-thalassemia intermedia (th3/+) C57BL/6 mice were intraperitoneally injected with 9 doses of iron dextran (1 g iron/kg body weight) over 2 weeks. In the iron overload condition, our data demonstrated a significant Furin mRNA reduction in WT and th3/+ mice. In addition, the liver furin protein level in iron-overloaded WT mice was significantly reduced by 70% compared to control WT mice. However, the liver furin protein in iron-overloaded th3/+ mice did not show a significant reduction compared to control th3/+ mice. The hepcidin gene (hepcidin antimicrobial peptide gene, Hamp1) expression was increased in iron-overloaded WT and th3/+ mice. Surprisingly, the liver hepcidin protein level and total serum hepcidin were not increased in both WT and th3/+ mice with iron overload, regardless of the increase in Hamp1 mRNA. In conclusion, we demonstrate furin downregulation in conjunction with Hamp1 mRNA-unrelated pattern of hepcidin protein expression in iron-overloaded mice, particularly the WT mice, suggesting that, not only the amount of hepcidin but also the furin-mediated physiological activity may be decreased in severe iron overload condition.
    Toxicology Reports 01/2015; 2:415-422. DOI:10.1016/j.toxrep.2015.01.004
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    ABSTRACT: Dengue is the most significant arthropod borne viral disease worldwide, and infection with the dengue virus causes a wide range of symptoms in humans, including bone marrow suppression. While the target cells of the virus remain poorly characterized, cells of the myeloid lineage have been shown to be important mediators of the disease. This study sought to determine whether erythroid precursor cells were susceptible to dengue virus infection, and whether erythroid cells from thalassemia trait carriers showed any protection against infection. Infection with a laboratory adapted high passage DENV-2 resulted in high levels of infection during certain stages of differentiation, and cells derived from thalassemia trait carriers showed significantly reduced susceptibility to dengue virus infection. Infection with low passage isolates resulted in only scattered cells showing evidence of infection, but high bystander apoptosis that was reduced by both a caspase 8 inhibitor and anti-tumor necrosis factor 1 receptor antibodies.
    Virology 12/2014; 471. DOI:10.1016/j.virol.2014.10.004 · 3.32 Impact Factor
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    ABSTRACT: Serum EPO concentration is related primarily to the rate of erythrocyte production and, under the stimulation of hypoxia, increases exponentially as hemoglobin (Hb) decreased. The level of EPO was determined in 141 subjects including 43 normal, 44 thalassemic patients and 54 thalassemic trait subjects. The EPO level was significantly higher in the thalassemic patients (54.8mU/ml in HbH disease [α thal1/α thal2;], 78.1mU/ml in HbH with Hb CS [α thal 1/CS]; 95.6mU/ml in β-thal/HbE splenectomized [BE(S)]; and 114.8mU/ml in β-thal/HbE non-splenectomized [BE(NS)]as compared with 12.0mU/ml in normal subjects. No significant differences were detected in thalassemic trait subjects. In addition, the levels of EPO in thalassemic patients is correlated significantly with the number of reticulocytes and the reticulocyte fractions especially the fraction of immature reticulocytes. Interestingly, the highest level of EPO/% retic ratio as indicated for EPO non-responder was detected in BE(NS) patients. However, the impaired reticulocytes maturation was found to be related significantly with the levels of TNF-α,IFN-γ,IL-10, and VEGF. Since, TNF-α, IFN-γ, IL-10 and VEGF are reported as the cytokines with erythropoietic inhibitory mediators, the variation of these cytokines in thalassemic environments may be associated to the anemic crisis in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.
    Blood Cells Molecules and Diseases 11/2014; 54(2). DOI:10.1016/j.bcmd.2014.11.007 · 2.65 Impact Factor
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    ABSTRACT: α(0)-Thalassemia occurs from a deletion of 2 linked α-globin genes and interaction of these defective genes leads to hemoglobin (Hb) Bart's hydrops fetalis, the most severe and lethal thalassemia syndrome. Identification of α(0)-thalassemia carriers is thus essential for the prevention and control program. An immunochromatographic (IC) strip test was developed for rapid screening of α(0)-thalassemia by testing for Hb Bart's in the blood samples using a specific monoclonal antibody against Hb Bart's. To evaluate its sensitivity and specificity, the IC strip test was assessed in a cohort with various thalassemia genotypes from 4 different laboratories in Thailand and Australia. The result showed 97% sensitivity in α-thalassemia carriers with 2 α-globin genes deletion and Hb H disease. This is, in particular, the useful rapid screening test for regions where β-thalassemia and homozygous Hb E are also common. Similar hematologic and Hb data make it impossible to address the concomitant inheritance of α(0)-thalassemia in these samples without polymerase chain reaction (PCR)-based techniques, leading to misdiagnosis of the risk of having Hb Bart's hydrops fetalis. However, α-globin genotyping should be carried out in samples with positive IC strip as positive reactivity was also observed in homozygous α(+)-thalassemia carriers who have 2 trans α-globin gene deletions. These results indicate that in combination with red blood cell indices, the IC strip test could rule out mass populations for further α(0)-thalassemia detection by PCR-based analysis. The Alpha Thal IC strip also has the potential to replace testing for Hb H inclusion bodies, as it appears to be more sensitive, specific, and less labor intensive. Copyright © 2014 Elsevier Inc. All rights reserved.
    Translational Research 11/2014; 165(6). DOI:10.1016/j.trsl.2014.10.013 · 5.03 Impact Factor
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    ABSTRACT: iPSC-based therapy is hardly conceivable in humans without prior validation in large preclinical animal models closely related to humans. We generated iPSCs from Macaca cynomolgus to evaluate the engraftment capacity of cy-iPSC-derived hematopoietic cells after autologous transplantation. We first optimized a hematopoietic differentiation protocol based on an EB approach and followed the differentiation process over 3 weeks by time-lapse FACS and CFC assays to identify emerging cells with hemangioblastic and hematopoietic phenotypes. Up to 20% of CD34 + cells emerged around Day 12 to 15 of differentiation; however, fewer than 1/200 CD34 + cells were able to form CFCs. We analyzed the expression of genes associated with mesodermal and hemato/endothelial differentiation during the 3 weeks of differentiation. Expression of hematopoietic genes was consistent with the emergence of hematopoietic cells as determined by FACS and CFC assays. To evaluate the engraftment potential of cy-iPSC-derived hematopoietic cells, we injected 106 cells into either the femur (12 mice) or the retroorbital sinus (10 mice) of sublethally irradiated NSG mice. At 5–7 weeks post-injection, hematopoietic engraftment was observed in 9/12 mice that received an intra-femoral injection and in none of the mice that received a retro-orbital injection. Up to 0.5% of mouse BM cells stained positive for a macaca CD45 + antibody. CD45 +CD14 + , CD45 +CD11b + myeloid and CD45 + CD20 + lymphoid macaca populations were detected. Large-scale production of hematopoietic cells is currently underway to enable the autologous transplantation of cells to donor monkeys in order to evaluate the capacity of these cells for short and long-term hematopoietic engraftment.
    ESGCT and NVGCT Collaborative Congress: The Hague-23 to 26 October; 10/2014
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    ABSTRACT: Pulmonary arterial hypertension is a life-threatening complication in thalassemia characterized by elevated pulmonary arterial pressure. Increased platelet activation is associated with this complication; however, its role remains unclear. Platelet activation in splenectomized β-thalassemia/hemoglobin E (Hb E) patients was measured using flow cytometric determination of P-selectin and activated glycoprotein (aGP) IIb/IIIa expression, and platelet-leukocyte aggregates (platelet-neutrophil, platelet-monocyte and platelet-lymphocyte aggregates). Tricuspid regurgitant velocity (TRV) was measured and used as an indicator of pulmonary arterial pressure. Plasma hemoglobin served as markers of hemolysis. Fifteen of 27 patients had elevated TRV (>2.5m/s). Platelet expression of P-selectin and aGPIIb/IIIa, and platelet-leukocyte aggregates were higher in thalassemia patients with elevated TRV than healthy control. Platelet-neutrophil aggregates increased in thalassemia patients with elevated TRV compared to patients with normal TRV. The increase in P-selectin and aGPIIb/IIIa expression induced by adenosine diphosphate (ADP) was higher in patients with elevated TRV than those with normal TRV. Platelet P-selectin expression and platelet-neutrophil aggregates correlated positively with TRV. Plasma hemoglobin levels in patients with elevated TRV were higher than those of the control subjects, and correlated with TRV. Thalassemia patients with elevated TRV have a further increase in platelet activation that correlates with hemolysis. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 10/2014; 135(1). DOI:10.1016/j.thromres.2014.10.010 · 2.45 Impact Factor
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    ABSTRACT: Background: Infection is one of the most common causes of death in β-thalassemia patients. This may be due in part to an underlying immunological abnormality. During the past decade, a subset of CD3+ T cells that express both CD4+CD8+ (DP) T-cells were discovered and have been described in several pathological conditions. However, phenotypic characterization of this unique T-lymphocyte subset in patients with β-thalassemia has not yet been investigated. Methods: Flow cytometry was used to determine the frequency of such CD4+CD8+(DP) cells in concert with frequencies of CD4+, CD8+, NKT cells and γδ-TCR T-lymphocytes in the peripheral blood of β-thalassemia/HbE patients. The frequencies of these lymphocyte subsets were compared with those in blood samples from healthy volunteers. Results: The results showed that the frequency of lymphocytes was significantly increased in splenectomized β-thalassemia/HbE patients but the frequencies of CD3+, CD4+ and CD8+ T-lymphocytes were not significantly different among the studied groups. However, analysis of unconventional T-lymphocytes revealed a significant increase in the frequency of CD4-CD8- in splenectomized β-thalassemia/HbE patients. The frequencies of CD4-CD8dim and CD4+CD8+ in β-thalassemia/HbE patients were similar to the controls. Further classification of the CD4+CD8+ cells revealed that β-thalassemia/HbE patient expressed significantly high levels of CD4brightCD8dim, with a marked increase found in non-splenectomized patients. Furthermore, significant increases in the frequency of γδ-TCR and NKT cells were also demonstrated in these splenectomized β-thalassemia/HbE patients. Conclusion: Our findings show the alteration of unconventional T-lymphocyte subsets in β-thalassemia/HbE patients, which may be responsible or may reflect the impaired immune response in β-thalssemia disease.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 09/2014; 32(3):261-269. DOI:10.12932/AP0426.32.3.2014 · 0.97 Impact Factor

Publication Stats

4k Citations
734.13 Total Impact Points


  • 1981-2015
    • Mahidol University
      • • Institute of Molecular Biosciences
      • • Department of Clinical Microscopy
      • • Department of Pharmacology
      • • Faculty of Medicine Siriraj Hospital
      • • Department of Pathology
      • • Faculty of Graduate Studies
      • • Department of Microbiology
      Krung Thep, Bangkok, Thailand
    • University of London
      Londinium, England, United Kingdom
  • 2011-2013
    • Chiang Mai University
      • Faculty of Medicine
      Amphoe Muang Chiang Mai, Chiang Mai, Thailand
    • Bangkok University
      Siayuthia, Bangkok, Thailand
  • 2008
    • University of North Carolina at Chapel Hill
      • Lineberger Comprehensive Cancer Center
      North Carolina, United States
  • 2004
    • Chulabhorn Research Institute
      • Laboratory of Biochemistry
      Krung Thep, Bangkok, Thailand
  • 2003
    • Murdoch Childrens Research Institute
      • Research Group for Heart Research
      Melbourne, Victoria, Australia
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 1993
    • National Institute of Science Technology and Development Studies
      New Dilli, NCT, India