curcumin and beta-Thalassemia

β-thalassemia is an inherited disorder that stems from a defect in beta-globin chain synthesis. Iron overload toxicity is one of the major clinical complications in β-thalassemia that may be due to a reduction in the hepcidin level. As a result, intestinal iron absorption increases and finally iron overload occurs. The current study aimed to investigate the effect of curcumin on serum iron status, ferritin, and transferrin in patients with β-thalas-semia intermedia.. This study was a randomized, controlled, double-blind clinical trial. Before and after the intervention period with curcumin, 5 ml blood was taken for the measurement of the entire index related to iron status.. Our results demonstrated the levels of serum iron (p-value < 0.001), ferritin (p-value = 0.002), and transferrin saturation (p-value < 0.001) significantly decreased in the curcumin group compared to placebo.. The data presented in this article show that curcumin supplementation would be effective in alleviating iron overload in patients with β-thalassemia intermedia.

Topics: beta-Thalassemia; Curcumin; Double-Blind Method; Ferritins; Humans; Iron; Iron Overload

Thalassemia intermedia is a subgroup of β-thalassemia which originates from mutations in the beta-globin gene. Zinc and copper play important roles in the metabolism. Due to its significant therapeutic effects, curcumin has led many studies to focus on curcumin. In a double-blind clinical trial study, 30 patients with beta-thalassemia intermedia with an age range of 20 to 35 years were randomly selected 1:1 to receive either curcumin or placebo for 3 months. Before and after the intervention period, 5 ml of blood was taken to determine the serum levels of zinc and copper. The laboratory tests were checked at baseline and at the end of the treatment. While the serum levels of zinc and zinc/copper significantly increased, the serum levels of copper decreased after 3 months of curcumin intake. In addition, on the basis of baseline characteristics, a negative correlation was found between zinc and body mass index and positive correlations were identified between copper with triglyceride and high-density lipoprotein. Also, the level of ferritin protein in the curcumin group compared to the placebo group showed a significant decrease after 3 months of curcumin use. Therefore, it could be concluded that curcumin might exert a net protective effect on copper toxicity in thalassemia intermedia patients. The investigation also implicated that curcumin represents an approach to regulating zinc homeostasis and may be useful as a complementary treatment of patients with thalassemia intermedia, especially in patients with zinc deficiency or low serum zinc/copper ratio. Clinical Trial Registration Number: IRCT20190902044668N1.

Topics: Administration, Oral; Adult; beta-Thalassemia; Blood Chemical Analysis; Capsules; Copper; Curcumin; Double-Blind Method; Ferritins; Humans; Iran; Male; Young Adult; Zinc

The most important cause of death in β-thalassemia major patients is organ dysfunction due to iron deposits. Non-transferrin bound iron (NTBI), labile plasma iron (LPI) and labile iron pool are redox-active forms of iron found in thalassemia. Iron chelation therapy is adopted to counteract the resulting iron overload. Extracts of green tea (GTE) and curcumin exhibit iron-chelating and antioxidant activities in iron-loaded cells and β-thalassemic mice. We have used our GTE-CUR drink to investigate the potential amelioration of iron overload and oxidative stress in transfusion-dependent β-thalassemia (TDT) patients. The patients were enrolled for a control group without and with GTE-CUR treatments (17.3 and 35.5 mg EGCG equivalent). Along with regular chelation therapy, they were daily administered the drink for 60 d. Blood samples were collected at the beginning of the study and after 30 d and 60 d for biochemical and hematological tests. Interestingly, we found a decrease of blood urea nitrogen levels (P < 0.05), along with a tendency for a decrease of NTBI and LPI, and a delay in increasing lipid-peroxidation product levels in the GTE-CUR groups. The findings suggest that GTE-CUR could increase kidney function and diminish redox-active iron in iron overloaded β-thalassemia patients.

Topics: Adolescent; Adult; Antioxidants; beta-Thalassemia; Blood Urea Nitrogen; Curcumin; Female; Humans; Iron Chelating Agents; Iron Overload; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Tea; Young Adult

Iron overload and oxidative stress are the major causes of serious complications and mortality in thalassemic patients. Our previous work supports the synergistic effects of antioxidant cocktails (curcuminoids or vitamin E, N-acetylcysteine, and deferiprone) in treatment of β-thalassemia/Hb E patients. This further 2-DE-based proteomic study aimed to identify the plasma proteins that expressed differentially in response to antioxidant cocktails.. Frozen plasma samples of ten normal subjects and ten β-thalassemia/Hb E patients at three-time points (baseline, month 6, and month 12) were reduced the dynamic range of proteome using ProteoMiner kit and separated proteins by two-dimensional gel electrophoresis. Differentially expressed proteins were identified using tandem mass spectrometry. Several plasma proteins were validated by ELISA and Western blot analysis.. Thirteen and 11 proteins were identified with altered expression levels in the curcuminoids- and vitamin E cocktail groups, respectively. The associations between vitronectin (VTN) expression and total bilirubin levels, as well as between serum paraoxonase/arylesterase 1 (PON1) expression and blood reactive oxygen species were observed. Validation results were consistent with proteomics results.. These plasma proteins may provide better understanding of the mechanisms underlying the therapeutic effects of antioxidant cocktails in thalassemic patients.

Topics: Acetylcysteine; Adult; beta-Thalassemia; Blood Proteins; Curcumin; Deferiprone; Drug Therapy, Combination; Female; Free Radical Scavengers; Gene Expression Regulation; Hemoglobin E; Humans; Male; Vitamin E

This study investigated the effects of curcumin, the active polyphenol in turmeric, on iron overload, hepcidin level, and liver function in β-thalassemia major patients. This double-blind randomized controlled clinical trial was conducted on 68 β-thalassemia major patients. The subjects were randomly divided into 2 groups to receive either 500 mg curcumin capsules (total: 1,000 mg) twice daily or placebo for 12 weeks. Dietary intakes and biochemical variables including hemoglobin, transferrin saturation, total iron binding capacity, nontransferrin bound iron (NTBI), ferritin, hepcidin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed at the beginning and end of the trial. Curcumin significantly reduced serum levels of NTBI (2.83 ± 1.08 compared with 2.22 ± 0.97 μmol/L, p = .001), ALT (42.86 ± 11.15 compared with 40.60 ± 9.89 U/L, p = .018), and AST (49.45 ± 12.39 compared with 46.30 ± 10.85 U/L, p = .002) at the end of the study. Based on analysis of covariance, a significant decrease was also observed in levels of NTBI (2.22 ± 0.97 vs. 2.55 ± 0.94 μmol/L, p = .026), ALT (40.60 ± 9.89 vs. 45.01 ± 10.42 U/L, p = .004), and AST (46.30 ± 10.85 vs. 50.99 ± 9.36 U/L, p = .009) in curcumin group in comparison with placebo group. There were no significant changes in hepcidin and other variables in any of the 2 groups. Curcumin administration alleviated iron burden and liver dysfunction by reducing NTBI, ALT, and AST levels in patients with β-thalassemia major.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; beta-Thalassemia; Curcuma; Curcumin; Double-Blind Method; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Iron; Iron Overload; Liver; Male; Young Adult

β-Thalassemia major, the most common inherited anemia in the world, is associated with imbalance in the oxidant-antioxidant system. The objective of this study was to evaluate the efficacy of curcumin supplementation on markers of oxidative stress in patients with β-Thalassemia.. This double-blind randomized controlled clinical trial was performed on 61 β-thalassemia major patients. Subjects in the curcumin group received two 500 mg curcumin capsules daily and patients in the placebo group took 2 placebo capsules daily for 12 weeks. Dietary intakes and biochemical parameters were assessed at the beginning and the end of intervention.. At the end of the study, serum malondialdehyde (MDA), total and direct bilirubin significantly decreased (p = 0.002, p < 0.001, and p < 0.001, respectively) and total antioxidant capacity significantly increased (p = 0.005) in the curcumin group. Based on the analysis of covariance, a significant reduction in MDA, total and direct bilirubin was also detected in the curcumin group when compared to the placebo group (p = 0.001, p = 0.039, and p = 0.013, respectively). Changes in hemoglobin, serum iron, ferritin, catalase, and vitamin E were not significant in any of the 2 groups.. Curcumin supplementation in combination with deferoxamin improved the antioxidant status in β-thalassemia major patients. Curcumin may be useful for the relief of metabolic complications in these patients.

Topics: Adult; Antioxidants; beta-Thalassemia; Biomarkers; Curcumin; Deferoxamine; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Malondialdehyde; Oxidative Stress; Young Adult

To evaluate the hematological profile, oxidative stress, and antioxidant parameters in beta-thalassemia/Hb E patients treated with curcuminoids for 12 months.. Twenty-one beta-thalassemia/Hb E patients were given 2 capsules of 250 mg each of curcuminoids (a total of 500 mg) daily for 12 months. Blood was collected every 2 months during treatment and 3 months after withdrawal and was determined for complete blood count, malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) in red blood cells (RBC), and non-transferrin bound iron (NTBI) in serum.. The increased oxidative stress in beta-thalassemia/Hb E patients was shown by higher levels of MDA, SOD, GSH-Px in RBC, serum NTBI, and lower level of RBC GSH. Curcuminoids administration resulted in improvement of all the measured parameters as long as they were administered. After 3 months withdrawal of treatment, all parameters returned close to baseline levels.. Curcuminoids may be used to ameliorate oxidative damage in patients with beta-thalassemia/Hb E disease.

Topics: Adolescent; Adult; Antioxidants; beta-Thalassemia; Curcumin; Enzyme Inhibitors; Female; Glutathione; Glutathione Peroxidase; Hemoglobin E; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Superoxide Dismutase; Young Adult

Thalassemic patients often exhibit high levels of oxidative stress and iron overload, which can lead to hazardous complications. Curcuminoids, extracted from the spice turmeric, are known to have antioxidant and iron-chelating properties and have been proposed as a potential upstream therapy of thalassemia. Here we have applied proteomic techniques to study the protein profile and oxidative damage in the plasma of β-thalassemia/Hb E patients before and after treatment with curcuminoids. In this study, 10 β-thalassemia/Hb E patients were treated with 500 mg curcuminoids daily for 12 months. The plasma protein profile and protein carbonyl content were determined at baseline, 6 and 12 months using two-dimensional fluorescence difference gel electrophoresis and carbonyl immunoblotting, respectively. Other hematological, clinical, and biochemical parameters were also analyzed. Twenty-six spots, identified as coagulation factors and proteins involved in iron homeostasis, showed significantly decreased intensity in thalassemic plasma, compared to those of normal subjects. Treatment with curcuminoids up-regulated the plasma levels of these proteins and reduced their oxidative damage. Serum non-transferrin bound iron, platelet factor-3 like activity, oxidative stress parameters and antioxidant enzymes were also improved after curcuminoids treatment. This study is the first proteomic study of plasma in the thalassemic state and also shows the ameliorating role of curcuminoids towards oxidative stress and iron overload in the plasma proteome.

Topics: Adult; Antioxidants; beta-Thalassemia; Curcuma; Dietary Supplements; Female; Hemoglobin E; Humans; Iron Chelating Agents; Iron Overload; Male; Middle Aged; Oxidative Stress; Plant Extracts; Protein Carbonylation; Proteome; Proteomics; Transferrin; Up-Regulation; Young Adult

Non-transferrin bound iron (NTBI) is found in plasma of β-thalassemia patients and causes oxidative tissue damage. Cardiac siderosis and complications are the secondary cause of death in β-thalassemia major patients. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising chelators used to get negative iron balance and improve life quality. DFP has been shown to remove myocardial iron effectively. Curcuminoids (CUR) can chelate plasma NTBI, inhibit lipid peroxidation and alleviate cardiac autonomic imbalance. Effects of CUR on cardiac iron deposition and function were investigated in iron-loaded mice. Wild type ((mu)β(+/+) WT) and heterozygous β-knockout ((mu)β(th-3/+) BKO) mice (C57BL/6) were fed with ferrocene-supplemented diet (Fe diet) and coincidently intervened with CUR and DFP for 2 months. Concentrations of plasma NTBI and malondialdehyde (MDA) were measured using HPLC techniques. Heart iron concentration was determined based on atomic absorption spectrophotometry and Perl's staining methods. Short-term electrocardiogram (ECG) was recorded with AD Instruments Power Lab, and heart rate variability (HRV) was evaluated using MATLAB 7.0 program. Fe diet increased levels of NTBI and MDA in plasma, nonheme iron and iron deposit in heart tissue significantly, and depressed the HRV, which the levels were higher in the BKO mice than the WT mice. CUR and DFP treatments lowered plasma NTBI as well as MDA concentrations (p <0.05), heart iron accumulation effectively, and also improved the HRV in the treated mice. The results imply that CUR would be effective in decreasing plasma NTBI and myocardial iron, alleviating lipid peroxidation and improving cardiac function in iron-loaded thalassemic mice.

Topics: Animals; beta-Thalassemia; Curcumin; Heart; Heart Rate; Humans; Iron; Iron Chelating Agents; Iron Overload; Iron, Dietary; Lipid Peroxidation; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Mice, Knockout; Transferrin

Non-transferrin bound iron (NTBI) is detectable in plasma of beta-thalassemia patients and participates in free-radical formation and oxidative tissue damage. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are iron chelators used for treatment of iron overload; however they may cause adverse effects. Curcuminoids (CUR) exhibits many pharmacological activities and presents beta-diketone group to bind metal ions. Iron-chelating capacity of CUR was investigated in thalassemic mice. The mice (C57BL/6 stain); wild type ((mu)beta(+/+)) and heterozygous beta-knockout ((mu)beta(th-3/+)) were fed with ferrocene-supplemented diet for 2 months, and coincidently intervened with CUR (200 mg/kg/day) and DFP (50 mg/kg/day). Plasma NTBI was quantified using NTA chelation/HPLC method, and MDA concentration was analyzed by TBARS-based HPLC. Hepatic iron content (HIC) and total glutathione concentration were measured colorimetrically. Tissue iron accumulation was determined by Perl's staining. Ferrocene-supplemented diet induced occurrence of NTBI in plasma of thalassemic mice as well as markedly increased iron deposition in spleen and liver. Treatment with CUR and DFP decreased levels of the NTBI and MDA effectively. Hepatic MDA and nonheme iron content was also decreased in liver of the treated mice whilst total glutathione levels were increased. Importantly, the CUR and DFP reduced liver weight index and iron accumulation. Clearly, CUR is effective in chelation of plasma NTBI in iron-loaded thalassemic mice. Consequently, it can alleviate iron toxicity and harmfulness of free radicals. In prospective, efficacy of curcumin in removal of labile iron pool (LIP) in hepatocytes and cardiomyocytes are essential for investigation.

Topics: Animals; beta-Thalassemia; Body Weight; Curcumin; Glutathione; Hemoglobins; Iron; Iron Chelating Agents; Iron Overload; Lipid Peroxidation; Liver; Mice; Organ Size