curcumin and Iron-Overload

Iron is an essential element in cellular metabolism that participates in many biochemical reactions. Nevertheless, iron overload in the body is the cause of damage in some organs including the liver, glands, brain, heart, gastrointestinal tract and lung. Iron chelation therapy could be considered an effective approach for removing excess iron. Deferoxamine, deferiprone and deferasirox are three common iron chelators in clinical practice but cause several side effects. In this context, the use of curcumin, a dietary phytochemical derived from turmeric, as a natural and safe antioxidant with iron-chelating activity may be a useful strategy for the management of iron overload. This review focuses on the deleterious effect of iron accumulation in different organs of the body as well as the therapeutic potential of curcumin against iron-induced toxicity.

Topics: Curcumin; Deferiprone; Deferoxamine; Humans; Iron; Iron Chelating Agents; Iron Overload; Pyridones

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

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

Malnutrition is common in haemodialysis patients and closely related to morbidity and mortality. We evaluated the effect of twelve weeks of supplementation with resveratrol and curcumin on recovery of bone and muscle mass and protein oxidation, lipid peroxidation on patients with chronic kidney disease and iron overload undergoing hemodialysis, we performed a randomized, double-blind, placebo-controlled trial.. We included a total of 40 patients, were randomly assigned to two groups, 20 to the group with antioxidant supplementation (Resveratrol + Curcumin) (Group A), treated with a daily oral dose of 500 mg of Resveratrol and 500 mg of Curcumin, and 20 to the control group treated with placebo (Group B).. Significant differences were found in the body composition of the patients between both groups. There was a significant difference in Body Mass Index (BMI) values (p = 0.002), fat percentage (p = 0.007), muscle mass (p = 0.01) bone mass (p = 0.01), as well as in the score of the subjective global evaluation (p = 0.03). Also differences were found between the basal and final serum levels of Triglycerides (TG) (p = 0.01), VLDL (p = 0.003). A significant decrease in the levels of serum ferritin (2003.69 ± 518.73 vs 1795.65 ± 519.00 ng/mL; p = 0.04). Nor were significant differences observed between the baseline and the final Thiobarbituric Acid Reactive Substances (TBARS) values (70.45 ± 69.21 vs 50.19 ± 32.62, p = 0.24). The same results was obtained for carbonyl values (2.67 ± 0.75 vs 2.50 ± 0.85; p = 0.50).. The present study is the first assay on patients with chronic kidney disease and iron overload that demonstrates the beneficial effects of combined supplementation with Curcumin and Resveratrol on muscle and bone mass. There was a significant decrease in circulating levels of ferritin, to finding that remarkably novel.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Bone Density; Curcumin; Dietary Supplements; Double-Blind Method; Female; Ferritins; Humans; Iron Overload; Male; Middle Aged; Muscles; Renal Dialysis; Renal Insufficiency, Chronic; Resveratrol; Triglycerides

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

Iron overload, which is common in patients with haematological disorders, is known to have a suppressive effect on haematogenesis. However, the mechanism for this effect is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage through an as-yet-unknown mechanism.. We established iron overload cell and mouse models. Mitochondrial reactive oxygen species (mROS) levels, autophagy levels and the SIRT3/SOD2 pathway were examined in the models and in the bone marrow of patients with iron overload.. Iron overload was shown to depress haematogenesis and induce mitochondrion-derived superoxide anion-dependent autophagic cell death. Iron loading decreased SIRT3 protein expression, promoted an increase in SOD2, and led to the elevation of mROS. Overexpression of SIRT3 reversed these effects. Curcumin treatment ameliorated peripheral blood cells generation, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy.. Our results suggest that curcumin exerts a protective effect on bone marrow by reducing mROS-stimulated autophagic cell death in a manner dependent on the SIRT3/SOD2 pathway.

Topics: Acetylation; Animals; Autophagy; Bone Marrow; Curcumin; Cytoprotection; Hematopoiesis; Humans; Iron Overload; Mice; Mitochondria; Reactive Oxygen Species; Sirtuin 3; Superoxide Dismutase

Iron is an essential element that involved in many vital physiological functions in fish, while excess iron concentration causes many toxic effects. Curcumin is a natural popular spice that used as a dietary supplementation and has iron chelating properties. This study was conducted to evaluate the effect of curcumin on iron toxicity in catfish (Clarias gariepinus). Also this study assess the antibacterial effect of curcumin against Vibrio anguillarum infection.. Clarias gariepinus were orally exposed to low and high doses of curcumin (40, 80 mg kg-1 fish) for 3 weeks. Fish were then exposed to 25 mg L-1 of ferric chloride as a source of iron toxicity for another 3 weeks. Some hematological parameters (Total and differential white blood cells count, total red blood cells count, hemoglobin concentration and hematocrit %) and biochemical parameters (Serum ferritin, transferrin, ALT, AST, protein and albumin) were assessed before and after exposure to iron. Iron residues in gills, spleen, liver, kidney, abdominal fats, gonads and muscles were also determined. Moreover the determination of fish survivability after bacterial challenge with Vibrio anguillarum was recorded.. Iron caused decrease in total white blood cells count (WBCs), increase in ferritin level and elevation in liver function enzymes (ALT and AST). However, the pretreatment of fish with curcumin significantly increased WBCs, lymphocyte percentage, ferritin level and protein and albumin concentrations with significantly decreased transferrin, ALT and AST levels. Also there were significant decreases in iron concentration in serum, kidney, gonads and muscle in both low and high curcumin pretreated groups compared to Fe group.. Results indicated a modulatory effect of curcumin against iron toxicity in catfish, also curcumin had an immune-stimulant effect against Vibrio anguillarum infection.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Catfishes; Curcumin; Dietary Supplements; Female; Fish Diseases; Iron; Iron Overload; Liver; Male; Vibrio; Vibrio Infections; Water Pollutants, Chemical

Topics: Animals; Antioxidants; Carcinogens; Cells, Cultured; Curcuma; Curcumin; Epithelial Cells; Ferric Compounds; Iron; Iron Overload; Liver; Liver Neoplasms; Oxidative Stress; Plant Extracts; Quaternary Ammonium Compounds; Rats

Excessive iron can generate reactive oxygen species (ROS), leading to oxidative stress that is closely associated with cardiovascular dysfunction. Iron overload was induced in male ICR mice by injection of iron sucrose (10mg/kg/day) for eight weeks. Iron overload was evidenced by increased serum iron indices. The mice developed increased blood pressure, impaired vascular function and blunted response of the autonomic nervous system. These effects were accompanied by increased malondialdehyde levels in various tissues, increased nitric oxide metabolites in plasma and urine, and decreased blood glutathione. Tetrahydrocurcumin (THU, 50mg/kg/day), deferiprone (or L1, 50mg/kg/day) or both was orally administered throughout the period of iron sucrose injection. The treatments significantly alleviated the deleterious cardiovascular effects of iron overload, and were associated with modulation of nitric oxide levels. An imbalance between endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in response to iron overload was normalized by THU, L1 or the combination treatment. Moreover, the treatment decreased the upregulated expression levels of gp91

Topics: Administration, Oral; Animals; Baroreflex; Curcumin; Deferiprone; Disease Models, Animal; Drug Therapy, Combination; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hypertension; Iron Chelating Agents; Iron Overload; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Pyridones

Iron overload is now recognized as a health problem in industrialized countries, as excessive iron is highly toxic for liver and spleen. The potential use of curcumin as an iron chelator has not been clearly identified experimentally in iron overload condition. Here, we evaluate the efficacy of curcumin to alleviate iron overload-induced hepatic and splenic abnormalities and to gain insight into the underlying mechanisms.. Three groups of male adult rats were treated as follows: control rats, rats treated with iron in a drinking water for 2 months followed by either vehicle or curcumin treatment for 2 more months. Thereafter, we studied the effects of curcumin on iron overload-induced lipid peroxidation and anti-oxidant depletion.. Treatment of iron-overloaded rats with curcumin resulted in marked decreases in iron accumulation within liver and spleen. Iron-overloaded rats had significant increases in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver and spleen when compared to control group. The effects of iron overload on lipid peroxidation and NO levels were significantly reduced by the intervention treatment with curcumin (P<0.05). Furthermore, the endogenous anti-oxidant activities/levels in liver and spleen were also significantly decreased in chronic iron overload and administration of curcumin restored the decrease in the hepatic and splenic antioxidant activities/levels.. Our study suggests that curcumin may represent a new horizon in managing iron overload-induced toxicity as well as in pathological diseases characterized by hepatic iron accumulation such as thalassemia, sickle cell anemia, and myelodysplastic syndromes possibly via iron chelation, reduced oxidative stress derived lipid peroxidation and improving the body endogenous antioxidant defense mechanism.

Topics: Animals; Chronic Disease; Curcumin; Iron; Iron Overload; Liver; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spleen

Necroptosis was reported as one backup way of programmed cell death when apoptosis was blocked, and the receptor interacting protein 1 was considered as the key necroptosis regulator protein. Here, we report the neuroprotective effects of curcumin which attenuates necroptosis. Primary cortical neurons were cultured and were injured by ferrous chloride, z.vad.fmk was applied to block apoptosis, curcumin was administrated to protect neurons, necrostatin-1 was applied to inhibit necroptosis if needed. Cell viability was measured by detecting lactate dehydrogenase activity in lysates of surviving cells, and assessed by cell counting kit-8. The expression of receptor interacting protein 1 was detected by immunoblot and immunofluorescence. Results showed that necroptosis mainly occurred in the concentrations of ferrous chloride ranging from 100 to 200μM, curcumin attenuated necroptosis in a dose-dependent manner. Furthermore, curcumin decreased expression of receptor interacting protein 1 in a dose- and time-dependent manner. Taken together, these findings suggest that curcumin protects against iron induced neurotoxicity in primary cortical neurons by attenuating necroptosis.

Topics: Animals; Apoptosis; Cells, Cultured; Cerebral Cortex; Curcumin; Dose-Response Relationship, Drug; Embryo, Mammalian; Ferrous Compounds; Iron Overload; Mice; Mice, Inbred C57BL; Necrosis; Neurons; Neuroprotective Agents

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

Iron is an essential micronutrient for human beings but its overload induces various diseases of liver, the main body storage site for iron, such as liver fibrosis. Curcumin is a natural polyphenol derived from turmeric and has been used widely. Its pharmacological action has attracted great attention in recent years. The apoptosis of rat cultured hepatocytes was induced by FeNTA (ferric nitrilotriacetate)-induced Iron overload. The present study was to examine the effect of curcumin at low concentrations on FeNTA-induced apoptosis of hepatocytes and elucidate the underlying mechanisms.. After the incubation of hepatocytes with 100 µmol/L FeNTA in the presence or absence of 1 - 10 µmmol/L of curcumin, a series of analyses were performed, including the analyses of hepatocytic apoptosis, the expressions of proteins relating with the regulations of cell apoptosis, caspase-3 activity, the production of reactive oxygen species (ROS) and nuclear factor NF-κB activity.. Curcumin reduced the FeNTA-induced hepatocytic apoptosis by 46.65% and significantly down-regulated the protein levels of Bcl-2 and Bcl-XL. In contrast, it had no effect on the protein levels of Bax and Bad. The curcumin treatment reduced FeNTA-caused production of ROS and caspase-3 activity by 45.01% and 59.71% respectively. And the NF-κB activity was also inhibited.. Curcumin at low concentrations reduces iron overload-caused hepatocytic apoptosis and NF-κB activity, the key regulatory transcription factor for the inflammation-related gene expression in cultured hepatocyte.

Topics: Animals; Apoptosis; Cells, Cultured; Curcumin; Hepatocytes; Iron Overload; NF-kappa B; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

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

On the basis of all the presented data, one can conclude that oxidative stress plays a major role in the pathophysiology of thalassemia and other congenital and acquired hemolytic anemias. Free extracellular (labile plasma iron, LPI) and intracellular (labile iron pool, LIP) iron species that have been identified in thalassemic blood cells are responsible for generation of oxidative stress by catalyzing formation of oxygen radicals over the antioxidant capacity of the cell. Consequently, there is a rationale for iron chelation to eliminate the free-iron species, which in this respect, act like antioxidants. In addition, antioxidants such as vitamin E and polyphenols are also capable of ameliorating increased oxidative stress parameters and, given together with iron chelators, may provide a substantial improvement in the pathophysiology of hemolytic anemias and particularly in thalassemia.

Topics: Antioxidants; Carica; Curcumin; Humans; Iron; Iron Chelating Agents; Iron Overload; Oxidation-Reduction; Oxidative Stress; Plant Preparations; Reactive Oxygen Species; Thalassemia

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

Here we report the synthesis, the characterization and a theoretical study on new glycosylated phenyl substituted beta-diketones; two classes of compounds are obtained according to the condensation reaction: central and side derivatives. Their iron(III) chelating ability is tested by means of UV-visible (UV-vis), potentiometric and NMR techniques. The conformation of central derivatives does not allow any metal chelation, while side derivatives bind iron(III) through the beta-dioxo moiety. The glycosyl moiety does not interact with metal ion but it helps to stabilize metal/ligand (1/3) complexes by means of hydrophylic interactions. The pK(a) of the ligands and the stability constants of their Fe(III) complexes are evaluated by means of UV-vis spectroscopy and potentiometry. A comparison with other iron-chelating agents, on the basis of lipophilicity and the pFe(III), is finally reported.

Topics: Crystallography, X-Ray; Curcumin; Drug Stability; Glycosylation; Humans; Hydrogen-Ion Concentration; Iron Chelating Agents; Iron Overload; Ketones; Ligands; Magnetic Resonance Spectroscopy; Molecular Structure; Potentiometry; Spectrophotometry; Spectrophotometry, Ultraviolet