scholarly journals Iron chelation by curcumin suppress both curcumin-induced autoghagy and cell death together with iron overload neoplastic transformation

2019 ◽  
Author(s):  
Nathan E. Rainey ◽  
Aoula Moustapha ◽  
Ana Saric ◽  
Gael Nicolas ◽  
Franck Sureau ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hereditary Hemochromatosis ◽  
Iron Chelation ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Cancer Field ◽  
Ferric Ammonium ◽  
Iron Complexation ◽  
Apoptotic Signal Transduction ◽  
Apoptotic Signal

Iron overload, notably caused by hereditary hemochromatosis, is an excess storage of iron in various organs which cause tissue damage and may promote tumorigenesis. To manage that disorder, free iron depletion can be induced by iron chelators like deferoxamine which are gaining interest also in the cancer field since iron stock could be a potent target for managing tumorigenesis. Curcumin, a well-known active substance extracted from the turmeric rhizome, has shown to be destabilizing endoplasmic reticulum and secondarily lysozomes, increasing mitophagy/autophagy and subsequent apoptosis. Recent findings show that cells treated with curcumin exhibit also a decrease in ferritin, which is consistent with it’s chemical structure and iron chelating activity. Here we investigated how curcumin would play on the intracellular effects of iron overload via Fe-Nitriloacetic acid or Ferric ammonium citrate loading in Huh-7 cells and explore consequences in terms of antioxidant activity, autophagy, or apoptotic signal transduction. With T51B and RL-34 epithelial cells experiments, we brought evidence that curcumin-iron complexation abolishes both curcumin-induced autophagy and apoptosis together with the tumorigenic action of iron overload.

scholarly journals Iron chelation by curcumin suppresses both curcumin-induced autophagy and cell death together with iron overload neoplastic transformation

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Nathan E. Rainey ◽  
Aoula Moustapha ◽  
Ana Saric ◽  
Gael Nicolas ◽  
Franck Sureau ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hereditary Hemochromatosis ◽  
Iron Chelation ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Cancer Field ◽  
Ferric Ammonium ◽  
Iron Complexation ◽  
Apoptotic Signal Transduction ◽  
Apoptotic Signal

Abstract Iron overload, notably caused by hereditary hemochromatosis, is an excess storage of iron in various organs that causes tissue damage and may promote tumorigenesis. To manage that disorder, free iron depletion can be induced by iron chelators like deferoxamine that are of increasing interest also in the cancer field since iron stock could be a potent target for managing tumorigenesis. Curcumin, a well-known active substance extracted from the turmeric rhizome, destabilizes endoplasmic reticulum, and secondarily lysosomes, thereby increasing mitophagy/autophagy and subsequent apoptosis. Recent findings show that cells treated with curcumin also exhibit a decrease in ferritin, which is consistent with its chemical structure and iron chelating activity. Here we investigated how curcumin influences the intracellular effects of iron overload via Fe-nitriloacetic acid or ferric ammonium citrate loading in Huh-7 cells and explored the consequences in terms of antioxidant activity, autophagy, and apoptotic signal transduction. In experiments with T51B and RL-34 epithelial cells, we have found evidence that curcumin-iron complexation abolishes both curcumin-induced autophagy and apoptosis, together with the tumorigenic action of iron overload.

Iron overload induced by ferric ammonium citrate triggers reactive oxygen species-mediated apoptosis via both extrinsic and intrinsic pathways in human hepatic cells

2015 ◽  
Vol 35 (6) ◽  
pp. 598-607 ◽  
Author(s):  
S-W Li ◽  
C-M Liu ◽  
J Guo ◽  
AM Marcondes ◽  
J Deeg ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ferric Ammonium

Background: Hepatic iron overload is common in patients with myelodysplastic syndromes undergoing hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better understand the mechanisms of iron overload-induced liver injury, we examined the effects of iron overload induced by ferric ammonium citrate (FAC) on oxidative stress and apoptosis signaling pathway in human hepatic cell line HH4. Methods and Results: Hepatic HH4 cells were exposed to FAC to force iron uptake, and cellular responses were determined. Incubation with 5 mM FAC resulted in increased intracellular iron content in a time-dependent manner. High concentration of FAC impaired cell viability and increased level of reactive oxygen species (ROS), and addition of antioxidant reagent such as glutathione or N-acetylcysteine dramatically reduced FAC-induced intracellular ROS generation. FAC overload significantly increased the phosphorylation of inhibitor of κB-α, p38 mitogen-activated protein kinase (MAPK), and nuclear factor κ light chain enhancer of activated B cells (NF-κB) p65 and promoted the nuclear translocation of NF-κB p65. Knockdown of Fas and Bid expression by small interfering RNA in iron-treated HH4 cells resulted in restoration of cell viability. Conclusions: We reported that FAC treatment is capable of inducing both extrinsic death receptor and intrinsic mitochondrial signaling pathway-mediated HH4 cells apoptosis through ROS-activated p38 MAPK and NF-κB pathways.

Chloroquine Modulates Arginase Activity by Limiting the Availability of Intracellular Mobile Iron Pool in Human Erythroid Cells.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1415-1415
Author(s):  
Efemwonkiekie W Iyamu ◽  
Harrison A Perdew ◽  
Gerald M Woods
Keyword(s):  
Iron Overload ◽  
Arginase Activity ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Erythroid Cells ◽  
Intracellular Iron ◽  
Iron Mobilization ◽  
Arginase 1 ◽  
Ferric Ammonium ◽  
Iron Pool

Abstract Increased iron absorption associated with intensive erythropoiesis and iron deposition as a result of continuous hemolysis contribute to cellular injuries in sickle cell disease (SCD). Iron overload seems to be a predisposing factor of disease severity and mortality in significant number of adult SCD and β-thalassemia patients. Indeed, there is now an impressive body of evidence indicating that increased intracellular iron pool might be the hallmark of mammalian cell susceptibility to oxidative stress. Recently, we showed that cysteine, in the presence of molecular iron, promotes arginase activity by driving the Fenton reaction in sickle erythrocytes (unpublished report). It has been suggested that the reduction of arginine bioavailability for nitric oxide (NO) production secondary to increased plasma arginase levels in SCD may contribute to severe pathophysiological derangements and increase mortality. We have previously shown that chloroquine (CQ), an anti-malarial and anti-rheumatoid drug, displays a linear competitive mode of inhibition on sickle erythrocyte arginase. In the present report we showed that treatment of cultured human erythroleukemic cells with 100 or 200 μM iron (ferric ammonium citrate) induced a significant increase in cell proliferation with corresponding increase in arginase activity. By using specific antibodies it was demonstrated that the increased arginase activity correlated with an increase in arginase-1 levels in the cells. Upon treatment of cells with 10 μM CQ, in the presence or absence of ferric ammonium citrate (FAC), the levels of arginase enzyme decreased by 33.5 % and 36.7 % respectively. In an effort to expand our understanding of the link between intracellular iron and CQ-mediated modulation of arginase activity, FAC-treated cells were co-incubated with 10 μM CQ for 48 hrs and the intracellular and membrane associated iron levels were determined by nitrilotriacetic acid (NTA)-ultracentrifugation assay. Our results indicate that CQ maximally enhanced the sequestration of intracellular iron by 39.3 % and that no effects of CQ were noted on the membrane associated iron levels. Further the level of ferritin was reduced by 29.4 % in CQ-treated cells in comparison with the FAC-treated cells alone as determined by immunosorbent assay. This data suggests that the observed diminished ferritin levels in the presence of CQ may be due to repression by translational regulators of ferritin function secondary to low intracellular iron levels, as evidenced in this study. Because treatment of cells with an intracellular iron chelator deferoxamine, in combination with CQ, caused a significant decrease in the levels of ferritin (60 % vs control; p = 0.006) and consequent reduction in ARG-1 levels (58.3 % vs control), we conclude that the sequestration of intracellular iron contributes in part to the CQ-mediated inhibition of arginase activity. We further investigated the effects of CQ on ferritin-Fe in a cell free system, reasoning that the effects of CQ on the intracellular iron pool may involve the modulation of iron mobilization from iron sources, such as ferritin (the main intracellular iron storage protein). To this end, purified human ferritin was incubated at predetermined time intervals in the presence or absence of 10–100 μM CQ at 37°C and the extent of NTA-mediated iron mobilization from ferritin was determined. Our results showed that CQ limits the mobilization of iron from ferritin in a dose-dependent manner. Our presented data demonstrate, for the first time, that CQ-mediated limitation of intracellular mobile iron pool modulates arginase activity as well as arginase-1 levels. We therefore speculate that an extreme increase in intracellular iron pool may result in the stimulation of arginase activity as observed in hemolytic diseases. In conclusion, we believe that our results represent a new and important improvement in understanding the pleiotropic effects of CQ on arginase activity, with specific reference to its participation on the limitation of intracellular iron availability in erythroid cells. Hence incorporating this template into structure-based enzyme design studies could lead to the production of new forms of efficient arginase inhibitors, which could be useful as therapeutic regimen in hemoglobinopathies and other iron overload related diseases.

Iron overload increases hepatic development ofPlasmodium yoeliiin mice

Parasitology ◽  
1996 ◽  
Vol 112 (2) ◽  
pp. 165-168 ◽  
Author(s):  
J. Goma ◽  
L. Rénia ◽  
F. Miltgen ◽  
D. Mazier
Keyword(s):  
Iron Overload ◽  
Malaria Infection ◽  
Iron Supplementation ◽  
Plasmodium Yoelii ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Ferric Ammonium ◽  
Hepatic Development

SummaryIron overload in BALB/c mice by treatment with ferric ammonium citrate promotes the hepatic development ofPlasmodium yoelii in vivoand invitro. This was the result of increased penetration of the parasite into hepatocytes since no effect was observed on parasite transformation or maturation. These results could explain why in endemic regions iron supplementation led, in certain studies, to an increase in clinical episodes of malaria and in the prevalence of malaria infection.

scholarly journals A study on the aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous fumarate, ferrous sulphate and ferric ammonium citrate, among the rural anaemic women, in the Indian spectrum

2019 ◽  
Vol 8 (12) ◽  
pp. 2751
Author(s):  
Moumita Hazra
Keyword(s):  
Ferrous Sulphate ◽  
Haemoglobin Concentration ◽  
Significant Rise ◽  
Demographic Characteristics ◽  
Health Concern ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Ferrous Fumarate ◽  
Ferrous Ascorbate ◽  
Ferric Ammonium

Background: Anaemia is a global health concern, associated with increased maternal and perinatal mortality, preterm delivery, low birth weight, extreme fatigue and impaired immune system; and controlled by oral haematinics; with a rise in haemoglobin concentration. The objective was to examine the various aspects of pharmacoepidemiology and pharmacohaemovigilance of oral haematinics, among the anaemic women population, in rural India.Methods: This was a multi-centre, retrospective, observational and analytical study of the hospital medical records of 250 anaemic patients, who were allocated into group A of 125 patients within 15-21 years and group B of 125 patients within 22-35 years. The patients were prescribed oral haematinics, containing 60 mg of elemental iron, thrice daily, with meals. The various aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous sulphate, ferrous fumarate and ferric ammonium citrate, including patients’ demographic characteristics, anaemic symptoms assessment, prescription patterns, and safety assessment, on 1st, 2nd, 3rd months and follow-up visits, were recorded and thoroughly analysed..Results: In groups A and B, the demographic characteristics of the patients were comparable; ferrous ascorbate was the most commonly prescribed oral haematinic, followed by ferrous sulphate, ferrous fumarate and ferric ammonium citrate, which controlled mild to moderate iron deficiency anaemia, with a gradual significant rise in haemoglobin concentration, in the successive 3 months; and adverse effects were observed to be statistically non-significant in either group.Conclusions: The different aspects of pharmacoepidemiology and pharmacohaemovigilance in the study established that the oral haematinics were reasonably beneficial and safe among the anaemic women population, in rural India.

THE EFFECT OF CERTAIN ORAL AND INJECTABLE IRON PREPARATIONS ON THE BLOOD OF BABY PIGS

1959 ◽  
Vol 39 (2) ◽  
pp. 193-201 ◽  
Author(s):  
H. Doornenbal
Keyword(s):  
Oral Iron ◽  
Ammonium Citrate ◽  
Normal Blood ◽  
Ferric Ammonium Citrate ◽  
Iron Dextran ◽  
Ferric Ammonium ◽  
Iron Sulphate

Haemoglobin levels, haematocrit values and erythrocyte counts were determined at weekly intervals from 3 to 45 days of age for 60 pigs which received iron in the form of: injectable iron-dextran (A); injectable iron-dextran (B); injectable ferric ammonium citrate; oral iron in the form of paste, or sods sprinkled with iron sulphate. The iron-dextran and ferric ammonium citrate compounds were administered at 3 days of age as single injections supplying 100 mgm. of iron and 30 mgm. of ferric ammonium citrate respectively. The paste was administered at 3, 10, 17 and 24 days of age. Sods were fed twice a week during the period of 3 days to 28 days of age.The sod treatment maintained normal blood values while the iron-dextran compounds and the paste resulted in values somewhat below normal, although visible evidence of anaemia was not apparent. Blood values for the group receiving ferric ammonium citrate were extremely low and two pigs on this treatment died at 42 and 60 days of age. Both exhibited severe anaemia.Significant differences were obtained in weaning weights. The heaviest pigs were those receiving sods; the lightest pigs those receiving injectable ferric ammonium citrate. The effect of the different treatments on growth was not apparent until after 21 days of age.

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