scholarly journals Evaluation of Ischaemia Modified Albumin as a Marker of Oxidative Stress in Beta Thalassemia Major Children

2021 ◽  
Vol 41 (1) ◽  
pp. 61-66
Author(s):  
K Jagadish Kumar ◽  
Smriti Bhagiratha ◽  
Prashanth Vishwanath
Keyword(s):  
Oxidative Stress ◽  
Cell Damage ◽  
Significant Negative Correlation ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Beta Thalassemia ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Regression Relationship ◽  
Healthy Control

Introduction: Iron overload in thalassemia catalyses the production of a variety of reactive oxygen species leading to cumulative cell damage. Ischemia modified albumin (IMA) is an end product of oxidative stress. It is imperative to pick up oxidative stress early in order to prevent the organ damage in thalassemia. Therefore this study was undertaken to estimate IMA levels and to see the correlation between ferritin and IMA to establish whether ferritin can be a proxy marker for oxidative stress. Methods: A total of 76 children were included in the study out of which 46 were diagnosed cases of β- Thalassemia major and 30 formed the healthy controls. Pre transfusion haemoglobin, AST, ALT, ferritin and IMA levels were estimated and compared with healthy control children. Correlation was drawn between haemoglobin, AST, ALT, ferritin with IMA. Results: There is significant elevation in the level of IMA and ferritin in children with Thalassemia major as compared to the healthy controls (p = < 0.001). There was a significant positive correlation between ferritin and IMA and a significant negative correlation between haemoglobin % and IMA. Regression relationship between ferritin and IMA established that IMA (ng/ mL) = 246.118 + 0.829 (Ferritin ng/dL). Conclusions: IMA levels were significantly elevated in β- thalassemia major children and correlated positively with ferritin levels. By establishing a regression relationship between ferritin and IMA levels, we can fairly estimate the levels of IMA. Hence, we can utilise ferritin as a proxy marker of oxidative stress instead of IMA.

scholarly journals Role of mitochondria-derived reactive oxygen species in microvascular dysfunction in chronic kidney disease

2018 ◽  
Vol 314 (3) ◽  
pp. F423-F429 ◽  
Author(s):  
Danielle L. Kirkman ◽  
Bryce J. Muth ◽  
Meghan G. Ramick ◽  
Raymond R. Townsend ◽  
David G. Edwards
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Heating ◽  
Reactive Oxygen ◽  
Microvascular Dysfunction ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Cutaneous Vasodilation

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Mitochondrial dysfunction secondary to CKD is a potential source of oxidative stress that may impair vascular function. This study sought to determine if mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in stage 3–5 CKD. Cutaneous vasodilation in response to local heating was assessed in 20 CKD patients [60 ± 13 yr; estimated glomerular filtration rate (eGFR) 46 ± 13 ml·kg−1·1.73 m−2] and 11 matched healthy participants (58 ± 2 yr; eGFR >90 ml·kg−1·1.73 m−2). Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution, and 2) the mitochondria- specific superoxide scavenger MitoTempo. Skin blood flow was measured via laser Doppler flowmetry during standardized local heating (42°C). Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum conductance achieved with sodium nitroprusside infusion at 43°C. Urinary isofuran/F2-isoprostane ratios were assessed by gas-chromatography mass spectroscopy. Isofuran-to-F2-isoprostane ratios were increased in CKD patients (3.08 ± 0.32 vs. 1.69 ± 0.12 arbitrary units; P < 0.01) indicative of mitochondria-derived oxidative stress. Cutaneous vasodilation was impaired in CKD compared with healthy controls (87 ± 1 vs. 92 ± 1%CVCmax; P < 0.01). Infusion of MitoTempo significantly increased the plateau phase CVC in CKD patients (CKD Ringer vs. CKD MitoTempo: 87 ± 1 vs. 93 ± 1%CVCmax; P < 0.01) to similar levels observed in healthy controls ( P = 0.9). These data provide in vivo evidence that mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in CKD and suggest that mitochondrial dysfunction may be a potential therapeutic target to improve CKD-related vascular dysfunction.

The Oxidative Status of Valinomycin-Resistant Normal and Thalassemic Red Cells (RBCs).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3191-3191
Author(s):  
Johnny Amer ◽  
Zipora Etzion ◽  
Robert M. Bookchin ◽  
Eitan Fibach
Keyword(s):  
Oxidative Stress ◽  
Oxidant Stress ◽  
Thalassemia Major ◽  
Oxidative Status ◽  
Normal Blood ◽  
Beta Thalassemia ◽  
Globin Genes ◽  
Before And After ◽  
Mercury Orange

Abstract Normal high-K+, low-Na+ RBCs, suspended in low-K+ media and permeabilized to K+ with valinomycin, become dehydrated from net loss of KCl and water. A very small fraction of light, normal RBC and larger fractions of light, sickle cell anemia (SCA) and beta-thalassemia RBC were found to be “valinomycin-resistant” (val-res) due to their Na+/K+ gradient dissipation (PNAS2000;97: 8050; BLOOD2000;96:24b). In thalassemia and SCA, although the primary lesions involve the globin genes, the major damage to the RBC membranes is mediated by oxidative stress. We previously showed (Cytometry2004;60:73) that thalassemic RBC have higher reactive oxygen species (ROS) and lower reduced glutathione (GSH) levels than normal RBC before or after in vitro oxidant stress (treatment with hydrogen peroxide). Here, we examined the oxidative status of val-res RBC from normal and beta-thalassemia major blood. RBC suspended in a plasma-like buffer containing 15 mM KCl and 10 mM valinomycin for 45 min were then layered on arabinogalactone (Larex) with density δ=1.091, and spun at 15,000 g for 30 min. Val-res cells were identified as the low density (δ<1.091 g/ml) RBCs recovered from the interphase layer. The percent val-res RBC in beta-thalassemic samples (n = 10), was 84-fold higher (4.2 ± 0.4% (mean ± SD), range 2.5 to 6.0%) than in normal samples (0.05 ± 0.06%, range 0.02 to 0.1%) (n =10). To determine the oxidative status of the RBC, the cells were washed with PBS and stained for intracellular contents of ROS and GSH, using 2′-7′-dichlorofluoresein and Mercury Orange, respectively. RBC were analyzed by flow cytometry, using gating based on size and granularity. The Mean Fluorescence Channel (MFC) for each fluorochrome was computed. The results showed that valinomycin treatment, per se, did not affect ROS and GSH contents: MFC of the stained un-fractionated RBC was similar before and after treatment with valinomycin, indicating that large changes in MCHC had little or no effect on these measurements. In addition, the unfractionated RBC had ROS and GSH values comparable to those of the high density (val-sensitive) RBC which were recovered from the pellet of valinomycin-treated RBC following Larex fractionation. Measurements on six normal and six beta-thalassemic blood samples indicated that in each case val-res RBC had higher ROS (3.5-10 fold) and lower GSH (2.5-8 fold) levels than the unfractionated RBC or the val-sensitive RBC of the same sample. Compared with val-res cells from normal blood, thalassemic val-res RBC had higher capacity to produce ROS (1.7-fold) and had a lower GSH level (1.5-fold) compared with normal val-res RBC. These results confirm that, as with SCA, beta-thalassemia blood contains a higher percent of val-res RBC than normal blood. They show, further, that (i) both normal and thalassemic val-res RBC have higher oxidative status than other cells (val-sensitive) in the same sample; and that (ii) thalassemic val-res RBC have higher oxidative status than val-res RBC in normal blood. The present results are consistent with the possibility that oxidative stress may contribute to the generation of val-res RBCs, but do not establish a cause-effect relationship. Further studies will be needed to elucidate the origin and significance of these cells.

In Vitro and In Vivo Antioxidant Effect of Fermented Papaya Preparation (FPP) on Blood Cells of Beta-Thalassaemia Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1766-1766
Author(s):  
Eitan Fibach ◽  
Johnny Amer ◽  
Ada Goldfarb ◽  
Eliezer Rachmilewitz
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Peripheral Blood ◽  
Thalassemia Major ◽  
Oxidative Status ◽  
Beta Thalassemia ◽  
Thalassemia Intermedia

Abstract In sickle cell anemia (SCD) and thalassemia, although the basic lesions are mutations in the globin genes, the pathophysiology involves oxidative stress-mediated cell damage in the bone marrow (ineffective erythropoiesis due to apoptosis of early erythroid precursors) and in the peripheral blood (chronic hemolysis of mature RBC). In addition, some patients develop thromboembolic complications and recurrent bacterial infections, the etiology of which is related at least in part, to documented oxidative stress in platelets and neutrophils (PMN), respectively. To study the presence and the role of oxidative stress in thalassemia and SCD, we adapted flow cytometry techniques for measuring the generation of Reactive Oxygen Species (ROS), the content of reduced glutathione (GSH), membrane lipid peroxidation and externalization of phosphatidylserine (PS) moieties in RBC, platelets and PMN. Cells derived from the peripheral blood of patients with beta-thalassemia major, intermedia or SCD showed increased oxidative status (increased ROS, lipid peroxidation and PS externalization, and decreased GSH) compared with their normal counterparts. Incubating fresh blood samples from patients with thalassemia major and thalassemia intermedia with 10 mg/ml FPP for 16 hours at 37oC reduced the oxidative status of RBC as well as platelets and PMN. Experiments carried out in normal and thalassemic mice (Th3/+, a mouse model of human beta-thalassemia intermedia demonstrated that mice treated for one week with 10 mg/ml FPP (dissolved in the drinking water) had reduced oxidative stress compared to control mice. The in-vivo effect of FPP was tested on 9 patients with beta-thalassemia (6 - major and 3 - intermedia) treated with 3 gr FPP per os three times a day for 12–15 weeks. Following the treatment, the ROS in RBC, platelets and PMN decreased and the GSH increased in all patients (see table). Six of these patients responded by a modest increase in RBC, reticulocytes and hemoglobin levels. These results suggest that FPP may have an important clinical efficacy as an antioxidant in thalassemia and sickle cell anemia. The in vivo effect of FPP treatment of beta-thalassemia patients Baseline After treatment n Mean ± SE Mean ± SE P-value* * Paired samples t-test RBC 9 324.07 ± 29.19 209.55 ± 23.65 0.001 ROS Platelets 9 223.73 ± 26.49 109.11 ± 8.71 0.001 PMN 9 222.72 ± 46.42 117.61 ± 8.98 0.045 RBC 9 55.37 ± 5.37 94.88 ± 3.71 0.001 GSH Platelets 9 59.41 ± 4.98 97.55 ± 5.26 <0.0001 PMN 9 58.29 ± 5.35 90.06 ± 5.87 0.005

scholarly journals Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Bhaskar Ponugoti ◽  
Guangyu Dong ◽  
Dana T. Graves
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cellular Response ◽  
Cell Damage ◽  
Cell Types ◽  
Biological Processes ◽  
Oxygen Species ◽  
Forkhead Transcription Factors ◽  
Foxo Transcription Factors

Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

scholarly journals Effects of Vitamin E on Transfusion Requirements in TransfusionDependent Beta-Thalassemia Patients

2018 ◽  
Vol 36 (3) ◽  
pp. 225
Author(s):  
Duangdee Trangsuwan ◽  
Malai Wongchanchailert ◽  
Ladda Mo-suwan ◽  
Thirachit Chotsampancharoen ◽  
Ruchaneekorn W. Kalpravidh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Glutathione Peroxidase ◽  
Thalassemia Major ◽  
Outcome Variable ◽  
Beta Thalassemia ◽  
Random Allocation ◽  
Oral Vitamin ◽  
Double Blind ◽  
Transfusion Requirements

Objective: To evaluate the volume of blood transfusion requirements as well as hemolytic and oxidative biochemical variables in transfusion-dependent β-thalassemia patients supplemented with vitamin E.Material and Methods: A prospective, double-blind, randomized, placebo-controlled, crossover study was undertaken between December, 2012 and September, 2014 in the Pediatric Clinic of Songklanagarind Hospital. The participants were β-thalassemia major and Hb E/β-thalassemia patients aged between 5 and 18 years. A random allocation sequence was generated to receiving either 6 months of vitamin E or placebo followed by a 3-month washout period and then switching to another drug for 6 months. The outcome variable measurements were the volumes of the transfused packed red cells, and the hemolytic and oxidative biochemical variables.Results: Thirty-nine patients were enrolled into the study. All of them had significantly low levels of vitamin E and reduced glutathione levels, as well as high levels of oxidative stress shown by significantly high levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase. The vitamin E levels became normal after the 6-month period of 200-400 milligram per day of oral vitamin E intake. All of the measured oxidative stress parameters did not improve except for the glutathione peroxidase level. Moreover, there was no difference in the volumes of transfused packed red cell requirements as well as hemolytic parameters like aspartate transaminase, lactate dehydrogenase, reticulocyte count and total bilirubin levels. Finally, no adverse reactions to oral vitamin E were found.Conclusion: Vitamin E supplementation normalized the vitamin E level and possibly partially reduced oxidative stress, but there was no difference in the volume of transfusion requirements or the hemolytic parameters in transfusion-dependent β-thalassemia patients.

scholarly journals Renal damages in patients with major β-thalassemia

2019 ◽  
Vol 9 (1) ◽  
pp. e02-e02
Author(s):  
Malihe Najafpour ◽  
Majid Farshdousti-Hagh ◽  
Ali Akbar Movasagpoor-Akbari ◽  
Abbas-Ali Hosein-Pour Feyzi ◽  
Majid Malaki
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Urine Analysis ◽  
Thalassemia Major ◽  
Cross Sectional Study ◽  
Iron Chelators ◽  
Beta Thalassemia ◽  
Sectional Study ◽  
Cross Sectional ◽  
Healthy Control

Introduction: Numerous studies have shown the presence of renal dysfunction in patients with beta thalassemia major (βTM). According to iron overload and effects on renal, evaluation of renal function in βTM can cause better control of them. Objectives: In this study, we evaluated renal function in children and adults with βTM. Patients and Methods: Sixty patients (38 male and 22 female) with βTM, and 60 healthy control subjects (25 males and 35 females), were participated in this cross-sectional study. Biochemical and urine analysis were conducted to evaluate renal function. Additionally, patients were classified based on the administration of iron chelators including deferoxamine (Desferal), deferiprone (L1), deferasirox (Exjade) and combination therapy. Results: Renal dysfunctions such as hyperfiltration and proteinuria were common findings in patients compared with the normal group. Hypercalciuria was found only in patients groups receiving Exjade. Hyperfiltration was detected in all patients. Proteinuria was no related to drug administration. Conclusion: We found a high percentage of our βTM patients who had renal dysfunction as evidenced by proteinuria and hyperfiltration.

scholarly journals Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

2021 ◽  
Vol 8 (4) ◽  
pp. 233-247
Author(s):  
Bhuvana Selvaraj ◽  
◽  
Sangeetha Soundararajan ◽  
Shettu Narayanasamy ◽  
Ganesan Subramanian ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Globin Gene ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Beta Thalassemia ◽  
Hemochromatosis Gene

<abstract> <p>Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with <italic>HFE</italic> gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of <italic>HFE</italic> variants among beta thalassemia cases and their effect on iron overload. The frequency of three <italic>HFE</italic> variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating <italic>HFE</italic> variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C <italic>HFE</italic> variant was absent in the present study. Iron overload was completely absent in the control cases among all three <italic>HFE</italic> genotypes. Hence it is inferred from the present investigation, analysis of <italic>HFE</italic> genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.</p> </abstract>

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