Beta-Thalassemia Minor and the risk of Atherosclerosis: the role of the erythrocytic oxidative stress and paraoxonase 1 levels as aggravating factors

ABSTRACT PURPOSE: Hemoglobin (Hb) F% is increased in up to half of beta-thalassemia (β-thal) carriers. Several polymorphisms have been linked to such variability in different populations, including HBG2 - 158(C>T) (Xmn I polymorphism) on chromosome 11. To determine the role of this polymorphism in such variability among Iraqi Kurds, the current study was initiated. MATERIALS AND METHODS: A total of 102 consecutive patients diagnosed as β-thal minor were enrolled. The enrollees had their diagnosis based on peripheral blood counts and high-performance liquid chromatography to determine HbA2 and HbF. All enrollees had their DNA extracted by phenol-chloroform method and Xmn I polymorphism detected by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The mean age (standard deviation [SD]) of the 102 enrollees was 25.4 (14.0) years, and the enrollees included 48 males and 54 females. Xmn I polymorphism was identified in heterozygous state in 46 (45.1%) patients and in homozygous state in one patient (0.98%). Thus, the minor allele frequency of this polymorphism was 0.235 in the studied group. There were no significant differences in red cell indices and HbA2% in carriers of the minor allele compared to noncarriers, while HbF% and absolute HbF concentrations were significantly higher in the former subgroup (P = 0.032 and 0.014, respectively). This polymorphism's contribution to HbF variability was found to be 5.8% in the studied sample. Furthermore, those with HbF ≥2% were 3.2 folds more likely to carry the minor allele. CONCLUSIONS: Xmn I polymorphism is frequently encountered in Iraqi Kurds with β-thal minor, and it is significantly associated with higher fetal hemoglobin in these patients.

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The Role of Oxidative Stress in the Etiopathogenesis of Gluten-Sensitive Enteropathy Disease

Journal of Medical Biochemistry ◽

10.1515/jomb-2017-0017 ◽

2017 ◽

Vol 36 (3) ◽

pp. 243-250 ◽

Cited By ~ 3

Author(s):

Mustafa Kaplan ◽

Ihsan Ates ◽

Mahmut Yüksel ◽

Yasemin Ozderin Ozin ◽

Muhammed Yener Akpinar ◽

...

Keyword(s):

Oxidative Stress ◽

Paraoxonase 1 ◽

Stress Index ◽

Control Group ◽

Gluten Free ◽

C Reactive Protein ◽

Serum Samples ◽

Reactive Protein ◽

Gluten Sensitive Enteropathy

SummaryBackground:The objective here is to examine the role of overall oxidative stress in the etiopathogenesis of gluten-sensitive enteropathy disease and its relationship with gluten free diet and autoantibodies.Methods:Eighty gluten-sensitive enteropathy patients and 80 control group participants were included in the study. As oxidative stress parameters, we researched total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), paraoxonase-1 and arylesterase parameters in the serum samples of gluten-sensitive enteropathy patients.Results:In comparison to the control group, gluten-sensitive enteropathy patients had lower TAS, paraoxonase-1 and arylesterase levels and gluten-sensitive enteropathy patients had considerable TOS and OSI levels. In contrast, patients who agreed to the gluten free eating routine had a higher OSI proportion and patients who did not conform to the gluten free eating regimen had a lower paraoxonase-1 level. An affirming reciprocation was de tected amidst TOS and OSI proportion and gluten-sensitive enteropathy autoantibodies and C-reactive protein levels and a negative correlation was found between arylesterase level and gluten-sensitive enteropathy autoantibodies.Conclusions:We observed oxidative stress levels to be higher in gluten-sensitive enteropathy patients contrasted with the control group. Oxidative stress level showed differences in gluten-sensitive enteropathy patients depending on gluten diet content and autoantibody positivity. In point of fact, C-reactive protein and gluten-sensitive enteropathy autoantibodies are identified with oxidative anxiety parameters resulting in the possibility that oxidative stress might be successful in the gluten-sensitive enteropathy pathogenesis.

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Correlation of Oxidative Stress with Serum Trace Element Levels and Antioxidant Enzyme Status in Beta Thalassemia Major Patients: A Review of the Literature

Anemia ◽

10.1155/2012/270923 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 42

Author(s):

Q. Shazia ◽

Z. H. Mohammad ◽

Taibur Rahman ◽

Hossain Uddin Shekhar

Keyword(s):

Oxidative Stress ◽

Trace Elements ◽

Antioxidant Enzymes ◽

Tissue Injury ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Beta Thalassemia Major ◽

Trace Element Levels ◽

Serum Trace Elements

Beta thalassemia major is an inherited disease resulting from reduction or total lack of beta globin chains. Patients with this disease need repeated blood transfusion for survival. This may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. The aim of this review is to scrutinize the relationship between oxidative stress and serum trace elements, degree of damage caused by oxidative stress, and the role of antioxidant enzymes in beta thalassemia major patients. The findings indicate that oxidative stress in patients with beta thalassemia major is mainly caused by tissue injury due to over production of free radical by secondary iron overload, alteration in serum trace elements and antioxidant enzymes level. The role of trace elements like selenium, copper, iron, and zinc in beta thalassemia major patients reveals a significant change of these trace elements. Studies published on the status of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione S-transferase in beta thalassemia patients also showed variable results. The administration of selective antioxidants along with essential trace elements and minerals to reduce the extent of oxidative damage and related complications in beta thalassemia major still need further evaluation.

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Evaluating the role of indirect bilirubin, urobilinogen and Shine and Lal index as an alternative screening tool for beta thalassemia minor

International Journal of Research in Medical Sciences ◽

10.5455/2320-6012.ijrms20150339 ◽

2015 ◽

Vol 3 (3) ◽

pp. 730

Author(s):

Ridham Khanderia ◽

Amit Agravat

Keyword(s):

Screening Tool ◽

Beta Thalassemia ◽

Indirect Bilirubin ◽

Thalassemia Minor

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ROLE OF BILIRUBIN AS A POTENTIALANTIOXIDANT IN SMOKERS

10.36106/ijsr/9801381 ◽

2021 ◽

pp. 43-45

Author(s):

Varshini. S ◽

A. Preethi ◽

G. Udayakumari

Keyword(s):

Oxidative Stress ◽

Antioxidant Properties ◽

Antioxidant Property ◽

Mean Value ◽

Paraoxonase 1 ◽

P Value ◽

College Hospital ◽

Chronic Respiratory Diseases ◽

The Mean

Introduction: Globally, smoking causes about 71% of lung cancer, 42% of chronic respiratory diseases and about 10% of cardiovascular disease. Smokers are exposed to potential oxidative damage. This leads to depletion of the body's defense against oxidative stress, like decrease in the levels of Paraoxanase -1. This study aimed to assess the antioxidant property of Bilirubin in comparison to Paraoxonase-1 in smokers. Materials & methods: This case control study was carried out at Govt. Kilpauk Medical College Hospital after obtaining ethical committee approval and informed consent. This study involves 2 groups with 90 chronic smokers and 90 apparently healthy individuals who are not smokers. Serum Bilirubin and Paraoxanase -1 levels were estimated and compared between these two groups. Correlation between Bilirubin and Paraoxanase-1 was analyzed. Statistical analysis was done using SPSS package version 20. Results: The mean value for Bilirubin is 0.566 +/- 0.03 mg/dL in smokers and 0.620 +/- 0.05 mg/dL in non-smokers. There is signicant difference in bilirubin levels between smokers and non smokers (p value - 0.049). The mean value for Paraoxonase-1 is 3.291+/- 0.75 ng/dL in smokers and 4.513+/- 0.96 ng/dL in non-smokers. There is signicant difference in Paraoxanase -1 levels between smokers and non smokers (p value - 0.025). The scatter plot between Paraoxanase -1 and Bilirubin shows no signicant correlation. Conclusion: The Paraoxanase -1 and Bilirubin values in smokers are considerably reduced in comparison to that of non-smokers. This shows that Paraoxanase -1 and Bilirubin exhibits potential antioxidant properties. Bilirubin estimation is inexpensive and can be easily measured rather than measuring other known antioxidants such as PON-1. Role of Bilirubin as a marker to detect the oxidative stress levels in smokers is established in this study

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OXIDATIVE STRESS MODULATES HEME LEVELS and INDUCES PEROXIREDOXIN-2 IN β THALASSEMIC ERYTHROPOIESIS as NOVEL CYTOPROTECTIVE RESPONSE

Blood ◽

10.1182/blood.v116.21.4266.4266 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4266-4266

Author(s):

Lucia De Franceschi ◽

Mariarita Bertoldi ◽

Maria Domenica Cappellini ◽

Luigia De Falco ◽

Sara Santos Franco ◽

...

Keyword(s):

Oxidative Stress ◽

Conflicts Of Interest ◽

Late Phase ◽

Erythroid Cell ◽

Beta Thalassemia ◽

Heme Oxygenase 1 ◽

Heme Binding ◽

Peroxiredoxin 2 ◽

Anti Oxidant

Abstract Abstract 4266 Beta thalassemia (β-thal) syndromes are worldwide distributed congenital red cell disorders. Increased levels of reactive-oxygen-species (ROS) have been reported to contribute to anemia in β-thal but the mechanism(s) involved in cell protection against ROS damage has only partially investigated. Here, we studied in vitro normal and β-thal erythropoiesis in erythroid cell cultures from CD34+ cells isolated from peripheral blood from adult normal volunteers and from homozygous (bcod39) b-thalassemia patients. We showed increased ROS production in β-thal erythropoiesis and we evaluated the effects of ROS on normal and β-thal erythropoiesis. We carried out a proteomic comparative study, validated by coupling Quantitative-Real time PCR and immunoblot analysis of the differently expressed proteins. We found down-regulation in expression of enzymes involved in heme catabolism such as biliverdin reductase (BVR) and heme-oxygenase-1 (HO-1) and up-regulation of two new cytoprotective cysteine-based-systems: peroxiredoxin-2 (Prx2) and heat-shock-protein-27 (HSP27), while catalase was similarly expressed in both cell models, suggesting a specific pattern of Px2 and HSP27 in β-thal erythroid precursors. We then measured heme levels and during b-thal-erythropoiesis and found that the synthesis of heme was biphasic displaying an increase of heme levels in early phase followed by a decrease in late phase in comparison to controls. Since heme synthesis depends on the erythroid δ-aminolevulinate-synthase isoform (ALAS-2), we evaluated ALAS-2 expression that resulted similar in normal and β-thal erythroid cells. We then showed that ALAS-2 activity was inhibited by both ROS and hemin, suggesting a possible role of heme and ROS levels in regulation of heme biosynthesis in β-thal cells. Since it has been reported that oxidative stress can up-regulate Prx2 expression and that genetically modified cells over-expressing Prx2 are generally more protected from severe oxidative stress (Phalen TJ et al 2006; Rabilloud T et al 2002; Kang SW et al 1998; Zhang P et al 1997), we have hypothesized a cytoprotective role of Prx2 in b-thal-erythropoiesis. We determined that the anti-oxidant Prx2 specifically binds hemin with high and affinity, most likely involving Prx2 cysteine residues. In order to look for the structural determinants to the binding, we noted that both ALAS-2 and Prx2 possess one and two cys-pro motifs, respectively. This motif is generally considered a heme sensor for many proteins able to bind heme and we propose that it could be responsible for heme binding in both enzymes. These data suggest a wider role of Prx2 as both anti-oxidant and heme-binding protein in protective stress-response-systems in β-thal erythropoiesis. Disclosures: No relevant conflicts of interest to declare.

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Role of epoetins in beta-thalassemia minor patients with solid tumors undergoing chemotherapy: Results of a retrospective analysis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.19600 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 19600-19600

Author(s):

H. J. Soto Parra ◽

E. Medula ◽

F. Latteri ◽

G. Lavenia ◽

P. Amadio ◽

...

Keyword(s):

Retrospective Analysis ◽

Solid Tumors ◽

Stage Iv ◽

Beta Thalassemia ◽

Second Line ◽

Mean Values ◽

Mild Anemia ◽

Thalassemia Minor ◽

Prospective Trials

19600 Background: β-Thalassemia minor (β-Tm) is the most common hereditary disorder in the Mediterranean region with a prevalence of 6% in Sicily. β-Tm is characterised by mild anemia (A). Therefore, we performed a retrospective analysis to evaluate the course of A in β-Tm pts with solid tumors (ST) undergoing chemotherapy (CT). Methods: β-Tm pts with ST were identified from our clinical record database [history and/or hemoglobin (Hb) A2 level > 3.3%]. Inclusion criteria were first-line or second-line CT after a CT-free interval of 6 mos. Exclusion criteria:concomitant radiotherapy (RT) , or previous RT to pelvic region, or active bleeding. Results: From July 2004 until the present day, 26 β-Tm pts with ST have been observed, and 23 fulfil the criteria of this analysis. The pt demography was as follows: median age, 56 years (range, 38–76 years); Males: 9 pts; PS 0/1: 19/4; stage IV: 10; types of cancers: breast 7, gastrointestinal 7, others 9; platinum containing regimen: 7. A was evaluated during first and second-line treatments in 19 and 4 pts, respectively. The mean values of Hb and the incidence of pts (%) with mild (from ≥10 and <12 gr/dl) or moderate (<10 gr/dl) A during CT, were as follows. No paradoxical effect of CT on the Hb level was observed. One pt received transfusions (Hb level, 7.8 gr/dl). Nine pts were treated with epoetin (darbepoetin alfa, 7 pts) and iron supplements due to worsening A (mean Hb value = 9 gr/dl ± 0.6): five pts experienced a ≥2 gr/dl increase in the Hb level at 8 weeks, one had >1 gr/dl, one had stable values = 9 gr/dl, and two pts had decreased values, i.e. < 8 gr/dl, and required transfusions. Conclusion: This analysis demonstrates that 70% of β-Tm pts with ST have mild or moderate A prior to CT. The A of β-Tm patients is worsened by CT and results in moderate A in 55% of the pts. Epoetins, particularly effectively ameliorate A when administered to pts with Hb levels of <10 gr/dl. This data suggests that epoetin treatment during CT may benefit β-Tm pts; however, prospective trials are required. No significant financial relationships to disclose. [Table: see text]

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Effect of Co Enzyme Q10 Alone or in Combination with Vitamin C on Lipopolysaccharide-Induced Brain Injury in Rats

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1483 ◽

2018 ◽

Vol 11 (3) ◽

pp. 1215-1226

Author(s):

Nabila A. El-Laithy ◽

Elsayed M.E. Mahdy ◽

Eman R. Youness ◽

Nermeen Shafee ◽

Mohamed S.S. Mowafy ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin C ◽

Brain Tissue ◽

Paraoxonase 1 ◽

Intraperitoneal Dose ◽

High Doses ◽

C 50 ◽

Histopathological Results ◽

The Impact

Our was to determine the impact of CoenzymeQ10 (Co Q10) and vitamin C alone or in combination on oxidative stress in brain tissue of rats during endotoxemia induced by single intraperitoneal dose of Lipopolysaccharide (LPS), 500µg/kg. Both CoQ10&vitamin C were given orally to rats with doses (200&100 mg/kg) respectively for 7successive days prior induction of endotoxemia .LPS injected, with Co Q10 with doses (100 &200 mg/kg) &vit. C (50&100 mg/kg).In addition CoQ10 and vitamin C together in doses (100&50 mg/kg) & (200&100 mg/kg) respectively were added to LPS-treated rats. Then euthanized 4 hours later. Histopathological assessment of brain tissue was done. Results: LPS injection induced oxidative stress in brain tissue, resulting in marked increase in malondiadehyde (MDA), nitrite (NO) and Amyloid beta (Aβ), while decreasing reduced glutathione (GSH), paraoxonase-1 (PON1) and brain derived neurotrophic factor (BDNF).CoQ10 and vit.C administration with doses(200&100 mg/ kg) before endotoxemia result in reduction of brain MDA, NO and Aβ, while increasing levels of GSH, PON1 and BDNF compared to controls. The addition of both Co Q10 &vit.C to LPS- treated rats lead to decrease of brain NO, MDA and Aβ, also increase of GSH, PON1 and BDNF. This effect was more obviouswith high doses, this due to the ameliorating effect of both CoQ10 and vit.C on oxidative stress of brain tissue during endotoxemia.This consisted with the histopathological results. Conclusion: this work focuses on the possible role of CoQ10 &vit.C as antioxidants in protecting brain tissue.

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