scholarly journals Decreased Iron Overload and Oxidative Stress in Transfusion Dependent Patients with Myelodysplastic Syndromes (MDS) with the Oral Iron Chelator Deferiprone

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4381-4381
Author(s):  
Drorit Merkel ◽  
Shelly Soffer ◽  
Kalman Filanovsky ◽  
Andrei Braester ◽  
Eitan Fibach ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Chelator ◽  
Low Risk ◽  
Primary Efficacy Variable ◽  
Primary Efficacy ◽  
Oxidative Stress Parameters ◽  
Daily Dose ◽  
And Oxidative Stress

Abstract Background: The majority of the patients with low risk myelodysplastic syndrome (MDS) become RBC-transfusion-dependent and thus symptoms resulting from iron overload and oxidative stress may develop. Yet, iron-chelation has not been part of the standard treatment for these patients. The purpose of this study was to assess the effect of deferiprone (L1), an iron chelator, on oxidative stress parameters in iron overloaded and blood dependent patients with low risk MDS. Methods: This work was supported by a grant from Apopharma. Nineteen low risk MDS patients were enrolled. Patients were classified as very low-, low- and intermediate-risk disease, according to the Revised International Prognostic Scoring System (IPSS-R). Inclusion criteria were a cumulative transfusion burden of >20 red blood cells (RBC) units and evidence of iron overload (serum ferritin >1,000 ng/mL). Deferiprone at a dose of up to a maximum dose of 100 mg/kg was administrated for 4 months. Blood samples were taken at baseline, at each monthly visit, and at the end of the study. The samples were tested for oxidative stress parameters: reactive oxygen species (ROS), phosphatidylserine (PS), glutathione (GSH) and membrane lipid peroxidation (LP); iron parameters: serum ferritin and cellular labile iron pool (LIP), and CBC. The primary efficacy variable as a measurement of oxidative stress was ROS. Student's t-test was applied for statistical analyses. Results: Patients (n=19) were treated with deferiprone in a daily dose of 25-100 mg/kg, median of 50 mg/kg/day. Eight patients received treatment for 120 days and completed the study. One of them had mild neutropenia that resolved after short discontinuation of the study drug and finished the study with no more complications. Eleven patients did not finish the study: eight patients due to gastrointestinal (GI) adverse effects, two patients withdrew their consent (one of them after mild neutropenia that resolved) and one patient was killed in a car accident. We thus had measurements of at least two time points for 16 of the patients. The median number of RBC transfusions during study period was 11 (2-20). The primary efficacy variable ROS, as a measurement of oxidative stress, was significantly decreased, in all three lineages: platelet, RBC and neutrophils (decrease of 32%, 33% and 32% respectively, each at P=0.001). Deferiprone administration was also associated with a reduction in other cellular markers of oxidative stress in RBC: PS, GSH, LP and LIP (decrease of 54%, 98%, 300%, and 42% respectively, each at P=0.001). No significant changes were observed in serum ferritin levels, likely due to the short treatment period in patients on repeated transfusion requirements. Conclusions: This is the first prospective study on chelation with Deferiprone in MDS patients. Our data provide preliminary evidence that administration of Deferiprone in a median daily dose of at 50 mg/kg can decrease iron-induced oxidative stress in iron-overloaded MDS patients. Of note, no events of agranulocytosis were observed. The future remains challenge is to prove that reduction in iron toxicity will eventually translate into a clinically meaningful improvement. Prof. Rachmilewitz who unfortunately passed away last year, had a significant contribution to the conception and design of this study. Disclosures No relevant conflicts of interest to declare.

Improvement of Oxidative Stress Parameters in MDS Patients with Iron Overload Treated with Deferasirox

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2675-2675 ◽  
Author(s):  
Eliezer Rachmilewitz ◽  
Drorit Merkel ◽  
Hussam Ghoti ◽  
Johnny Amer ◽  
Arnon Nagler ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Blood Cells ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Ros Generation ◽  
Iron Species ◽  
Oral Iron Chelator

Abstract Introduction: Using flourescence markers, evidence for oxidative stress has been documented by flow cytometry in red cells (RBC) and other blood cells of patients with congenital and acquired hemolytic anemias (e.g. thalassemia, sickle cell anemia, hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria) as well as in myelodysplatic syndrome (MDS) (Eur. J. Hematol. 79:463,2008). These data included increased generation of reactive oxygen species (ROS) concomittant with a decrease in the cellular content of the major antioxidant reduced gluthatione (GSH), and increased membrane lipid peroxidation. Oxidative stress in these anemias is thought to be mainly due to the accumulation of non-transferrin-bound iron (NTBI) which affects iron homeostasis and results in excess extra-cellular and intra-cellular labile pools: labile plasma iron (LPI) and cellular labile iron pool (LIP) (Cytometry 73:22,2008), respectively, catalyzing ROS generation. The presence of these free iron components is correlated with the severity of hemolysis and the subsequent repetitive blood transfusions, resulting in iron-overload. The purpose of the present study was to measure changes in parameters of iron-overload and oxidative stress in iron-overloaded patients with MDS following treatment with the oral iron-chelator Deferasirox. Patients and Methods: Fifteen patients–5 males and 10 females-(mean age 66 ± 13 years) with “low risk” MDS (IPSS < 1.0) received Deferasirox 20 mg/kg/day (12 patients) or 4–6 mg/kg/day (3 patients) due to side effects mainly gastrointestinal, increased creatinine and rash, for an average period of 95 days (63–163 days). All of them had evidence of iron-overload. Their mean number of transfusions was 65 ± 62, and mean ferritin levels before treatment was 3008 ± 1797 ng/ml. ROS, GSH, lipid peroxidation, LIP and LPI were measured every 3–4 weeks, in RBC, platelets and polymorphonuclear leukocytes (PMN). Blood cell counts, hemoglobin levels and serum ferritin were assayed simulteneously. Results: There was a statistically significant decrease in ROS (28%, p=0.006), lipid peroxidation (138%, p=0.008) and the LIP (23%, p=0.004) of RBC, concomittant with an increase in GSH (123%, p=0.001). GSH was also increased in platelets (48%, p=0.008) and PMN (72%, p=0.001), and LIP decreased in platelets (23%, p=0.004). In 8 patients the mean initial LPI levels of 0.39 units decreased to 0.12 units (p=0.028). There were no significant changes in hemoglobin levels or in any of the other types of blood cells. Mean serum ferritin levels increased in 8 patients by 964 ± 927 ng/ml and decreased in the rest by 1432 ± 1267 ng/ml. Discussion: The results clearly demonstrate that administration of Deferasirox to iron-overloaded MDS patients for a mean period of 3 months resulted in a significant decrease in parameters of oxidative stress mainly in RBC and platelets and in intra-(LIP) and extra-cellular (LPI) species of free iron. Serum ferritin, a major parameter in the assessment of the severity of iron-overload, was increased in 8 patients in the present study, similar to previously reported findings of increased ferritin levels at 12 months following iron chelation with Deferasirox (Am. J. Hematol.83:611–3, 2008). However, unlike iron stored in ferritin, the major risk of iron-overload is the presence of excess extra and intracellular iron species (LPI and LIP) which are playing an important role in ROS generation and consequent membrane damage in blood cels and in other major organs.. These preliminary data suggest that treatment with Deferasirox,, a once-a-day oral iron chelator, reduced the toxic iron species and several parameters of oxidative stress in iron overloaded MDS patients. Furthermore, the novel methodologies applied in this study may be useful for evaluating the severity of the iron-overload and for monitoring the efficacy of iron chelation therapy. Additional studies assessing the correlation of these changes to the long-term morbidity, mortality, and quality of life are definitely warranted in this patient population.

Abnormal red blood cell morphological changes in thalassaemia associated with iron overload and oxidative stress

2019 ◽  
Vol 72 (8) ◽  
pp. 520-524 ◽  
Author(s):  
Pornthip Chaichompoo ◽  
Ariz Qillah ◽  
Pornpan Sirankapracha ◽  
Jirada Kaewchuchuen ◽  
Poramate Rimthong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Cell ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Red Blood Cell ◽  
Morphological Changes ◽  
Normal Subjects ◽  
Target Cells ◽  
Red Cell ◽  
And Oxidative Stress

AimsIron overload is a major factor contributing to the overall pathology of thalassaemia, which is primarily mediated by ineffective erythropoiesis and shorter mature red blood cell (RBC) survival. Iron accumulation in RBCs generates reactive oxygen species (ROS) that cause cellular damage such as lipid peroxidation and RBC membrane deformation. Abnormal RBCs in patients with thalassaemia are commonly known as microcytic hypochromic anaemia with poikilocytosis. However, iron and ROS accumulation in RBCs as related to RBC morphological changes in patients with thalassaemia has not been reported.MethodsTwenty-one patients with thalassaemia, including HbH, HbH with Hb Constant Spring and β-thalassaemia/HbE (splenectomy and non-splenectomy) genotypes, and five normal subjects were recruited. RBC morphology was analysed by light and scanning electron microscopy. Systemic and RBC iron status and oxidative stress were examined.ResultsDecreased normocytes were observed in the samples of patients with thalassaemia, with RBC morphological abnormality being related to the type of disease (α-thalassaemia or β-thalassaemia) and splenic status. Target cells and crenated cells were mainly found in splenectomised patients with β-thalassaemia/HbE, while target cells and teardrop cells were found in non-splenectomised patients. Patients with thalassaemia had high levels of serum ferritin, red cell ferritin and ROS in RBCs compared with normal subjects (p<0.05). Negative correlations between the amount of normocytes and serum ferritin (rs=−0.518, p=0.011), red cell ferritin (rs=−0.467, p=0.025) or ROS in RBCs (rs=−0.672, p<0.001) were observed.ConclusionsIron overload and its consequent intracellular oxidative stress in RBCs were associated with reduce normocytes in patients with thalassaemia.

Omega-3 fatty acids and mood stabilizers alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration

2016 ◽  
Vol 32 (2) ◽  
pp. 519-528 ◽  
Author(s):  
Lara M. Gomes ◽  
Milena Carvalho-Silva ◽  
Letícia J. Teixeira ◽  
Joyce Rebelo ◽  
Isabella T. Mota ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Mood Stabilizers ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Oxidative Stress Parameters ◽  
And Oxidative Stress ◽  
Stress Parameters

Behavior and oxidative stress parameters in rats subjected to the animal's models induced by chronic mild stress and 6-hydroxydopamine

2021 ◽  
Vol 406 ◽  
pp. 113226
Author(s):  
Talita Tuon ◽  
Sandra S. Meirelles ◽  
Airam B. de Moura ◽  
Thayse Rosa ◽  
Laura A. Borba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative Stress Parameters ◽  
6 Hydroxydopamine ◽  
And Oxidative Stress ◽  
Stress Parameters

Protective role of Sterculia tragacantha aqueous extract on pancreatic gene expression and oxidative stress parameters in streptozotocin-induced diabetic rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
Jennifer Chidera Awurum ◽  
Sunday Amos Onikanni ◽  
Adedotun Adefolalu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Protective Role ◽  
Diabetic Rats ◽  
Gene Expressions ◽  
Ki 67 ◽  
Oxidative Stress Parameters ◽  
And Oxidative Stress ◽  
Stress Parameters

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.

scholarly journals The Influence of Probiotic Supplementation on Depressive Symptoms, Inflammation, and Oxidative Stress Parameters and Fecal Microbiota in Patients with Depression Depending on Metabolic Syndrome Comorbidity—PRO-DEMET Randomized Study Protocol

2021 ◽  
Vol 10 (7) ◽  
pp. 1342
Author(s):  
Oliwia Gawlik-Kotelnicka ◽  
Anna Skowrońska ◽  
Aleksandra Margulska ◽  
Karolina H. Czarnecka-Chrebelska ◽  
Igor Łoniewski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Study Protocol ◽  
Bifidobacterium Longum ◽  
White Blood Cells ◽  
Fecal Microbiota ◽  
Probiotic Supplementation ◽  
Oxidative Stress Parameters ◽  
And Oxidative Stress ◽  
Stress Parameters

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. The paper presents a study protocol that aims to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammatory and oxidative stress markers, as well as fecal microbiota in adult patients with depressive disorders depending on the co-occurrence of metabolic syndrome. The trial will be a four-arm, parallel-group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks (ClinicalTrials.gov identifier: NCT04756544). The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, high-density lipoprotein (HDL) cholesterol, triglycerides, fasting glucose, fecal microbiota composition and the level of some fecal microbiota metabolites, as well as serum inflammatory markers and oxidative stress parameters. The proposed trial may establish a safe and easy-to-use adjunctive treatment option in a subpopulation of depressive patients only partially responsive to pharmacologic therapy.

MS97 THE EFFECT OF THE n-3/n-6 PUFA RATIO ON THE TRANSFORMATION OF POSTPRANDIAL STATE PROATHEROGENIC LDL PHENOTYPE AND OXIDATIVE STRESS PARAMETERS

2010 ◽  
Vol 11 (2) ◽  
pp. 129-130 ◽  
Author(s):  
A. Dembinska-Kiec ◽  
M. Malczewska-Malec ◽  
H. Roche ◽  
I. Leszczynska-Golabek ◽  
J. Hartwich ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pufa Ratio ◽  
Oxidative Stress Parameters ◽  
Postprandial State ◽  
And Oxidative Stress ◽  
Stress Parameters
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