Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload

2015 ◽  
Vol 96 (3) ◽  
pp. 318-326 ◽  
Author(s):  
Mohsen S. Elalfy ◽  
Maha M. Saber ◽  
Amira Abdel Moneam Adly ◽  
Eman A. Ismail ◽  
Mohamed Tarif ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Vitamin C ◽  
Iron Overload ◽  
Thalassemia Major ◽  
Iron Chelators ◽  
Efficacy And Safety ◽  
Tissue Iron

Role of Vitamin C As an Adjuvant Therapy with Different Iron Chelators in Young β-Thalassemia Major Patients: Safety and Efficacy in Relation to Tissue Iron Overload

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4046-4046 ◽  
Author(s):  
Mohsen Saleh Elalfy ◽  
Maha Saber ◽  
Amira Adly ◽  
Eman Ismail ◽  
Mohamed Tarif ◽  
...  
Keyword(s):  
Vitamin C ◽  
Iron Overload ◽  
Cardiac Mri ◽  
Thalassemia Major ◽  
Hemoglobin Level ◽  
Iron Chelators ◽  
Vitamin C Deficiency ◽  
Tissue Iron ◽  
Vitamin C Supplementation ◽  
Laboratory Variables

Abstract Background: Treatment with antioxidants may neutralize the deleterious effects of oxidative damage by reactive oxygen species generated from labile plasma iron. Vitamin C has been known to increase the efficacy of desforaxamine (DFO). Few studies examined the influence of vitamin C supplementation in iron overloaded β-thalassemia major (β-TM) patients with oral chelators. Aim: To determine the beneficial effects of Vitamin C as an adjuvant to iron chelators in children and adolescents with β-TM and its relation to tissue iron overload. Methods: A randomized prospective study registered on ClinicalTrials.gov (NCT02083575) included 100 patients with β-TM recruited from the regular attendees of Thalassemia center. Inclusion criteria were β-TM patients 2-18 years with serum ferritin (SF) >1000-2500 ng/ml on regular transfusion-chelation therapy receiving the standard doses of Desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) in a ratio1:1:1. All the enrolled patients had vitamin C deficiency. Exclusion criteria included patients suffered from insulin-dependent diabetes, clinical cardiac and/or advanced liver disease. The thalassemia patients received vitamin C in a dose of 100 mg daily. Patients were followed-up for 6 months with assessment of transfusion frequency and index, complete blood count, vitamin C levels, serum iron, total iron binding capacity (TIBC), SF and transferrin saturation (Tsat), liver iron content (LIC) and cardiac magnetic resonance imaging T2* before and after therapy were assessed. Results: Laboratory variables at baseline were similarly distributed among patients receiving different iron chelating agents. Upon comparing baseline and post-therapy clinical and laboratory variables among the studied β-thalassemia patients; transfusion index was significantly decreased after 6 months of vitamin C therapy (p=0.03) and the number of transfused patients <3 weeks dropped from 66% to 57% although the difference did not reach a significant level. Hemoglobin level improved (p<0.01). SF, Tsat and LIC were significantly lower after treatment than baseline levels (p=0.048, p<0.01 and p=0.035, respectively). Cardiac MRI T2* and vitamin C levels increased 6 months after treatment (p=0.025 and p<0.001, respectively). Vitamin C supplementation to patients receiving DFO had significantly lowest transfusion index (p=0.035) with significant improvement in hemoglobin level and cardiac MRI T2* as well as decreased SF, Tsat and LIC (p<0.01). Patients on DFP or DFX showed non-significant improvement in hematological and radiological variables. Vitamin C level was negatively correlated to transfusion index, SF and LIC (p<0.01). Neither serious adverse reactions related to the chelators nor to Vitamin C administration have been reported. Conclusions: Vitamin C in a dose of 100 mg, as an adjuvant therapeutic agent increased the efficacy of DFO in reducing iron burden in the moderately iron overloaded B-TM with vitamin C deficiency; it showed marginal improvement with DFP and DFX. Higher doses of vitamin C therapy might be tried with evaluation of possible additional adverse events. Disclosures No relevant conflicts of interest to declare.

Circulating miRNAs and tissue iron overload in transfusion-dependent β-thalassemia major: novel predictors and follow-up guide

2021 ◽  
Author(s):  
Nashwa El-Khazragy ◽  
Safa Matbouly ◽  
Demiana H. Hanna ◽  
Nievin Ahmed Mahran ◽  
Sally Abdallah Mostafa ◽  
...  
Keyword(s):  
Iron Overload ◽  
Thalassemia Major ◽  
Circulating Mirnas ◽  
Tissue Iron

scholarly journals Treating thalassemia major-related iron overload: the role of deferiprone

2012 ◽  
pp. 119 ◽  
Author(s):  
Vasili Berdoukas ◽  
Farmaki ◽  
Carson ◽  
Wood ◽  
Coates
Keyword(s):  
Iron Overload ◽  
Thalassemia Major

Analysis of efficacy and safety of two iron chelators in type 1 Gaucher disease patients with iron overload

2013 ◽  
Vol 108 (2) ◽  
pp. S64-S65 ◽  
Author(s):  
Blanca Medrano-Engay ◽  
María Pilar Irún ◽  
Luis Sarría ◽  
Pilar Alfonso ◽  
Miguel Pocoví ◽  
...  
Keyword(s):  
Iron Overload ◽  
Gaucher Disease ◽  
Iron Chelators ◽  
Efficacy And Safety ◽  
Type 1 Gaucher Disease

scholarly journals Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 5027-5035 ◽  
Author(s):  
Sara Gardenghi ◽  
Maria F. Marongiu ◽  
Pedro Ramos ◽  
Ella Guy ◽  
Laura Breda ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Content ◽  
Iron Absorption ◽  
Regulatory Gene ◽  
Regulatory Genes ◽  
Ineffective Erythropoiesis ◽  
Transfusion Therapy ◽  
Iron Distribution ◽  
Tissue Iron

Abstract Progressive iron overload is the most salient and ultimately fatal complication of β-thalassemia. However, little is known about the relationship among ineffective erythropoiesis (IE), the role of iron-regulatory genes, and tissue iron distribution in β-thalassemia. We analyzed tissue iron content and iron-regulatory gene expression in the liver, duodenum, spleen, bone marrow, kidney, and heart of mice up to 1 year old that exhibit levels of iron overload and anemia consistent with both β-thalassemia intermedia (th3/+) and major (th3/th3). Here we show, for the first time, that tissue and cellular iron distribution are abnormal and different in th3/+ and th3/th3 mice, and that transfusion therapy can rescue mice affected by β-thalassemia major and modify both the absorption and distribution of iron. Our study reveals that the degree of IE dictates tissue iron distribution and that IE and iron content regulate hepcidin (Hamp1) and other iron-regulatory genes such as Hfe and Cebpa. In young th3/+ and th3/th3 mice, low Hamp1 levels are responsible for increased iron absorption. However, in 1-year-old th3/+ animals, Hamp1 levels rise and it is rather the increase of ferroportin (Fpn1) that sustains iron accumulation, thus revealing a fundamental role of this iron transporter in the iron overload of β-thalassemia.

scholarly journals Ameliorating Iron Overload in Intestinal Tissue of Adult Male Rats: Quercetin vs Deferoxamine

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Arwa A. El-Sheikh ◽  
Shimaa Hamed Ameen ◽  
Samaa Salah AbdEl-Fatah
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Adult Male ◽  
Caspase 3 ◽  
Iron Chelation ◽  
Male Rats ◽  
Albino Rats ◽  
Tissue Iron ◽  
Small Intestinal

Objective. The aim of our study is to compare the role of the new natural alternative (Quercetin) with the current iron-chelation therapy (Deferoxamine (DFO)) in the effect of iron overload on small intestinal tissues and to investigate the possible underlying molecular mechanisms of such toxicity. Methods. Forty-two adult male albino rats were divided into six groups: control groups, DFO, Quercetin, iron overload, iron overload+DFO, and iron overload+Quercetin groups. Animals received daily intraperitoneal injection of Deferoxamine (125 mg /kg), Quercetin (10 mg/kg), and ferric dextran (200 mg/kg) for 2 weeks. Results. Iron overloaded group showed significant increase in serum iron, total iron binding capacity (TIBC), transferrin saturation percentage (TS %) hepcidin (HEPC), serum ferritin, nontransferrin bound iron (NTBI), and small intestinal tissues iron levels. Iron overload significantly increased the serum oxidative stress indicator (MDA) and reduced serum total antioxidant capacity (TAC). On the other hand, iron overload increased IL6 and reduced IL10 in small intestinal tissues reflecting inflammatory condition and increased caspase 3 reactivity indicating apoptosis and increased iNOs expressing cell indicting oxidative stress especially in ileum. In addition, it induced small intestinal tissues pathological alterations. The treatment with Quercetin showed nonsignificant differences as compared to treatment with DFO that chelated the serum and tissue iron and improved the oxidative stress and reduced tissue IL6 and increased IL10 and decreased caspase 3 and iNOs expressing cells in small intestinal tissues. Moreover, it ameliorated the iron overload induced pathological alterations. Conclusion. Our study showed the potential role of Quercetin as iron chelator like DFO in case of iron overload induced small intestinal toxicity in adult rats because of its serum and tissue iron chelation, improvement of serum, and small intestinal oxidative stress, ameliorating iron induced intestinal inflammation, apoptosis, and histopathological alterations.

The role of ferroptosis in organ toxicity

2021 ◽  
pp. 096032712110529
Author(s):  
Fatemeh Yarmohammadi ◽  
A Wallace Hayes ◽  
Gholamreza Karimi
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Overload ◽  
Iron Chelators ◽  
Ros Generation ◽  
Oxygen Species ◽  
Organ Toxicity ◽  
Ros Accumulation ◽  
Dependent Form ◽  
Novel Therapeutic

Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities.

scholarly journals Myth Busters: Dietary Supplements and COVID-19

2020 ◽  
Vol 54 (8) ◽  
pp. 820-826 ◽  
Author(s):  
Kathleen K. Adams ◽  
William L. Baker ◽  
Diana M. Sobieraj
Keyword(s):  
Social Media ◽  
Vitamin D ◽  
Vitamin C ◽  
Dietary Supplements ◽  
Evidence Based ◽  
Efficacy And Safety ◽  
Treatment And Prevention ◽  
Social Media Platforms ◽  
Evidence Based Guidelines

News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.

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