scholarly journals Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 863
Author(s):  
Fatou Gueye Tall ◽  
Cyril Martin ◽  
El hadji Malick Ndour ◽  
Camille Faes ◽  
Indou Déme Ly ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
G6pd Deficiency ◽  
Clinical Severity ◽  
Oxidative Stress Biomarkers ◽  
Antioxidant Genes ◽  
Stress Biomarkers ◽  
Alpha Thalassemia ◽  
The Impact

Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs2333227) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity.

scholarly journals Oxidative Stress Biomarkers in Urine of Metal Carpentry Workers Can Be Diagnostic for Occupational Exposure to Low Level of Welding Fumes from Associated Metals

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3167
Author(s):  
Flavia Buonaurio ◽  
Maria Luisa Astolfi ◽  
Daniela Pigini ◽  
Giovanna Tranfo ◽  
Silvia Canepari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Occupational Exposure ◽  
Oxidation Products ◽  
Control Group ◽  
Welding Fumes ◽  
Oxidative Stress Biomarkers ◽  
Limit Values ◽  
Stress Biomarkers ◽  
Specificity And Sensitivity ◽  
The Impact

Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO2Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.

Maternal Oxidative Stress, Placental Morphometry, and Fetal Growth in Diabetic Rats Exposed to Cigarette Smoke

2018 ◽  
Vol 26 (9) ◽  
pp. 1287-1293 ◽  
Author(s):  
Yuri K. Sinzato ◽  
Estela M. Bevilacqua ◽  
Gustavo T. Volpato ◽  
Rogelio E. Hernandez-Pando ◽  
Marilza V. C. Rudge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Fetal Growth ◽  
Fetal Development ◽  
Oxidative Stress Biomarkers ◽  
Junctional Zone ◽  
Pregnant Rats ◽  
Stress Biomarkers ◽  
Vascular Walls ◽  
The Impact

The diabetic syndrome affects pregnancy, contributing to placental functional and structural disruptions and impaired fetal development, with many reports indicating tobacco-associated morbidity and perinatal mortality. In our study, an experimental rat model of diabetes and cigarette smoke exposure in pregnant rats was used to determine the impact of the combination of diabetes and exposure to cigarette smoke during pregnancy on maternal oxidative stress biomarkers and placental and fetal development. Diabetes was induced by streptozotocin, and dams were exposed to cigarette smoke by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Four groups of dams were studied: nondiabetic (C, control) and diabetic (D) exposed to filtered air and nondiabetic (CS) and diabetic (DS) exposed to cigarette smoke prior to and during pregnancy. Maternal oxidative stress biomarkers, placental morphology, and fetal growth were determined close to term. The combination of diabetes and cigarette smoke resulted in elevated maternal blood glucose levels and increased number of small fetuses. Placentas from the DS group showed increased junctional zone and decreased labyrinthine area. The morphological alterations were characterized by extensive vascular congestion, thickness, and hyalinization of the vascular walls, numerous decidual cells with abundant glycogen, and macrophages with cytoplasmic inclusions of hemosiderin. Additionally, they showed increased glycogen accumulation and junctional zone structural derangement with ectopic giant cells. No alterations were observed in maternal oxidative stress status. Thus, our result suggests that diabetes makes pregnant rats more susceptible to the adverse effects of exposure to cigarette smoke on placental morphometry and fetal growth.

Association between Oxidative Stress, Genetic Factors, and Clinical Severity in Children with Sickle Cell Anemia

2018 ◽  
Vol 195 ◽  
pp. 228-235 ◽  
Author(s):  
Céline Renoux ◽  
Philippe Joly ◽  
Camille Faes ◽  
Pauline Mury ◽  
Buse Eglenen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Genetic Factors ◽  
Clinical Severity

Antioxidant Vitamins C and E Supplementation Does Not Improve the Hemolytic Profile of Sickle Cell Anemia Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1063-1063
Author(s):  
Martha Mariana A S Arruda ◽  
Grazielle Mecabo ◽  
Celso Arrais Rodrigues ◽  
Sandra S Matsuda ◽  
Iara Baldim Rabelo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
Antioxidant Vitamins ◽  
Vitamin Supplementation ◽  
Indirect Bilirubin ◽  
Severe Deficiency ◽  
The Impact

Abstract Abstract 1063 Background: Erythrocytes of sickle cell anemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells, and oxidative stress seems to play a significant role in the pathophysiology of this disease. In erythrocytes, oxidative stress primarily affects the membrane and results in hemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants, which could prevent adhesion and phagocytosis of oxidized erythrocytes. Aims: To evaluate the impact of antioxidant vitamins C (vitC) and E (vitE) supplementation in the hemolytic profile in SCA patients. Patients and methods: Homozygous SCA or S-β-thalassemia patients, over 18 years, were randomly assigned to receive VitC 1,400 mg + VitE 800 mg per day or placebo, administered orally for 180 days. Pregnant women and patients with iron overload out of chelation therapy were excluded. Patients were evaluated clinically and blood samples were collected at days 0 and 180 for complete blood count, automated reticulocyte count, indirect bilirubin, lactate dehydrogenase (LDH), haptoglobin, uric acid, and serum levels of VitC and VitE. Results: Overall, 83 patients were enrolled (44 vitamins, 39 placebo). The median (range) age was 27 (18–68) years, and 53 (64%) were female. There were no significant differences between the two groups as regards clinical complications of SCA or baseline laboratorial tests and serum vitC and vitE. Sixty percent of the patients were VitC deficient (30% with severe deficiency), 70% were VitE deficient (33% with severe deficiency) and 44% were deficient in both vitamins. Vitamin supplementation increased VitC from 27.2 to 62.6 μMol/L (p<0.0001) and VitE from 13.9 to 20.2 μMol/L (p<0.0001). No changes in vitC or vitE were observed in patients receiving placebo. No significant changes in hemoglobin levels, hematocrit, mean corpuscular volume were observed in either group. However, patients receiving vitamin supplementation presented a significant increase in the median reticulocyte count (from 152 to 195 ×106/μL, p=0.01), LDH (from 396 to 425 U/L, p=0.018), indirect bilirubin (from 1.45 to 1.73 mg/dL, p<0.0001), and uric acid (from 4.75 to 5.15 mg/dL, p=0.02), and a decrease in the haptoglobin levels (from 3.95 to 3.45 mg/dL, p=0.06). Conclusion: Supplementation with vitamins C and E did not improve anemia and, surprisingly, increased markers of hemolysis in patients with SCA and S-β-thalassemia. The exact mechanisms to explain our findings and their clinical significance remain to be determined. Disclosures: No relevant conflicts of interest to declare.

Impact of α-Gene Deletions and β-Globin Cluster Haplotypes on Biological Parameters at Baseline and on Hydroxyurea in Children with Sickle Cell Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 10-10
Author(s):  
Francoise Bernaudin ◽  
Cécile Arnaud ◽  
Annie Kamdem ◽  
Serge Pissard ◽  
Isabelle Hau ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Linear Regression Analysis ◽  
Phenotypic Expression ◽  
Monogenic Disease ◽  
Multivariate Linear Regression Analysis ◽  
Biological Parameters ◽  
Alpha Thalassemia ◽  
The Impact

Abstract Despite being a monogenic disease, sickle cell anemia (SCA) is remarkably heterogeneous in its phenotypic expression. Additional genetic polymorphisms such as α-thalassemia co-inheritance and β-globin haplotypes have a recognized influence. Alpha-thalassemia reduces HbS polymerization and decreases hemolysis by lowering intracellular hemoglobin concentration. The three major β-globin haplotypes, Senegal (SEN), Benin (BEN) and Bantu/Central African Republic (CAR), have been reported to affect disease severity, in part by influencing baseline HbF levels, but no studies in large cohorts have so far compared the biological parameters in patients with these haplotypes. The haplotype BEN is largely predominant in the US, and patients are often compound heterozygotes for two different haplotypes, whereas the haplotype CAR is rarely observed. In Africa, environmental, nutritional and infectious factors make it difficult to distinguish the role of haplotypes in modulating hematological characteristics. In France, SCA-patients are frequently homozygous for the different haplotypes, rendering the comparison of hematological parameters possible. The aim of this study was to evaluate the impact of α-thalassemia and β-haplotypes on the biological parameters recorded at baseline and on hydroxyurea (HU). SCA-patients from the Créteil pediatric cohort with available assessment of α genes, β-haplotypes and baseline parameters were included in this study (n=578). Alpha-thalassemia was present in 254/578 (44%), with 191 (33%) having one deleted gene and 63 (10.9%) two. CAR/CAR homozygosity was present in 216 (37.4%), BEN/BEN in 140 (24.2%) and SEN/SEN in 69 (11.9%) patients, and 153 (26.5%) had other haplotypes (Cameroon, atypical or heterozygous). The presence of α-Thal was significantly more frequent (p<0.001) in CAR/CAR (121/216; 56%) than in BEN/BEN (43/140; 31%) and SEN/SEN (19/69, 28%). Univariate correlations of biological parameters with the number of α genes and β-haplotypes are shown in Table 1. Multivariate linear regression analysis showed that HbF% was positively correlated with SEN (β=0.152,p=0.003) and negatively with CAR (β=-0.189,p<0.001) whereas hemoglobin and LDH were inversely correlated with the number of α genes (β=-0.225,p<0.001 and β=0.201,p<0.001) and CAR haplotypes (β=-0.230,p<0.001 and β=0.171,p=0.001) respectively. As shown in Table 2, hemoglobin and HbF% were significantly lower in CAR/CAR than in BEN/BEN, and lower in BEN/BEN than in SEN/SEN, independently of the α-Thal status. Whereas LDH was not different in patients with α-Thal, LDH was significantly higher in CAR/CAR than in BEN/BEN and SEN/SEN in those with no α-Thal. Thus, the CAR/CAR patients with no α-Thal have the most severe hemolytic anemia with the lowest Hb and highest LDH levels. Hydroxyurea was given to 168 SCA-children at the median age of 6.6 years and the median dose of 26 mg/kg/day for at least one year between February 1993 and December 2014. The biological parameters were recorded when HbF % increase was maximal, and the delta (D) values from the initiation levels were calculated. Indications for HU were frequent VOC/ACS (n=101), severe anemia (n=23), and normalized TCD in patients with abnormal-TCD history (n=44). Alpha-Thal was present in 72/168 (56%), while CAR/CAR was present in 77/168 (46%), BEN/BEN in 41/168 (24%), and SEN/SEN in 12/168 (7%). Table 3 summarizes the biological parameters and D changes. Paired analysis showed significant changes in all parameters whatever the β-haplotypes and α gene number. Leukocytes, neutrophils, platelets, reticulocytes, bilirubin, LDH were lower while hemoglobin, MCV and HbF were higher. However, the SEN/SEN/α-Thal group was too small to show significance. On HU, parameters were no longuer significantly different between CAR/CAR patients and the others, except for hemoglobin that remained significantly lower (p=0.008) in CAR/CAR patients without α-Thal than in BEN/BEN and SEN/SEN patients. In conclusion, patients without α-Thal and with the CAR/CAR β-haplotype have the most severe hemolytic anemia at baseline. Despite a significant increase of their hemoglobin level on HU, they remain the most severely anemic patients. These results may explain some of the discrepancies observed between US and French studies, in particular regarding the effects of HU on cerebral vasculopathy for which the correction of anemia is crucial. Disclosures No relevant conflicts of interest to declare.

G6PD deficiency, absence of α-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4314-4317 ◽  
Author(s):  
Françoise Bernaudin ◽  
Suzanne Verlhac ◽  
Sylvie Chevret ◽  
Martine Torres ◽  
Lena Coic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
G6pd Deficiency ◽  
Odds Ratio ◽  
Multivariate Logistic Regression Analysis ◽  
Multivariate Logistic Regression ◽  
Alpha Thalassemia ◽  
Independent Risk Factors ◽  
First Time

AbstractStroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). This study aimed at defining predictive factors for abnormally high velocities (≥ 2 m/sec) based on the Créteil pediatric sickle cell anemia (SCA) cohort composed of 373 stroke-free SCA children. α genes and β-globin haplotypes were determined. Biologic parameters were obtained at baseline. α-thalassemia was present in 155 of 325 and G6PD deficiency in 36 of 325 evaluated patients. TCD was abnormal in 62 of 373 patients. Multivariate logistic regression analysis showed that G6PD deficiency (odds ratio [OR] = 3.36, 95% confidence interval [CI] 1.10-10.33; P = .034), absence of alpha-thalassemia (OR = 6.45, 95% CI 2.21-18.87; P = .001), hemoglobin (OR per g/dL = 0.63, 95% CI 0.41-0.97; P = .038), and lactate dehydrogenase (LDH) levels (OR per IU/L = 1.001, 95% CI 1.000-1.002; P = .047) were independent risk factors for abnormally high velocities. This study confirms the protective effect of alpha-thalassemia and shows for the first time that G6PD deficiency and hemolysis independently increase the risk of cerebral vasculopathy.

scholarly journals Elucidation of the liver proteome in response to an antioxidant intake in rabbits

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akeem Babatunde Sikiru ◽  
Arunachalam Arangasamy ◽  
Stephen Sunday Acheneje Egena ◽  
Sejian Veerasamy ◽  
Ippala Janardhan Reddy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Chlorella Vulgaris ◽  
Protein Extraction ◽  
Drug Candidate ◽  
Antioxidant Enzyme Activities ◽  
Proteomic Profiling ◽  
Oxidative Stress Biomarkers ◽  
Antioxidant Genes ◽  
Stress Biomarkers

Abstract Background Antioxidant intakes are one of the most cherished dietary approaches for the management of oxidative stress-induced liver damages. These antioxidants exist as the bioactive compounds present in plants and other natural sources functioning in varieties of ways from acting as direct scavengers of the free radicals to acting as the modifiers of genes and proteins expressions. Chlorella vulgaris is one of such antioxidants; it is a unicellular microalga and a rich source of polyphenols which has been reported for its capacity of reducing oxidative stress by upregulation of antioxidant genes. However, there are scarce reports on its effect on antioxidant protein expressions and functions in the liver. This situation necessitates untargeted proteomic profiling of the liver due to the antioxidant intakes as carried out in this present study. Sixteen laboratory weaner rabbits of 8 weeks old with initial average bodyweight of 1060 ± 29.42 g were randomly divided into two groups (n = 8 per group); the first group served as control while the second served as the treatment group were used for this study. Results After a period of 120 days daily consumption of 500 mg of Chlorella vulgaris biomass per kg bodyweight of the rabbit models, the animals were sacrificed and their livers were harvested followed by protein extraction for the untargeted proteomic profiling using LC-MS/Orbitrap Fusion Tribrid™ peptides quantifier and sequencer. Also, there was an assessment of the oxidative stress biomarkers in the liver and serum of the rabbits. Five-hundred and forty-four (544) proteins were identified out of which 204 were unique to the control, 198 were unique to the treatment group, while 142 were common to both groups of the rabbits. Antioxidant proteins commonly found in both groups were upregulated in the treatment group and were significantly associated with oxidative stress-protective activities. There was a reduction in oxidative stress biomarkers of the supplemented group as indicated by the assessment of the liver malondialdehyde concentrations (p < 0.05), total antioxidant capacities (p < 0.05), and antioxidant enzyme activities (p < 0.05). Similarly, these biomarkers were significantly reduced in the serum of the supplemented rabbits (p < 0.05). Conclusion The study concluded that Chlorella vulgaris is an antioxidant agent that could be suitable for reducing liver oxidative stress damage and it is a potential drug candidate for protecting the liver against oxidative stress damages as revealed in the rabbit models.

High LDH Level, G6PD Deficiency and Absence of alpha-Thalassemia Are Significant Independent Risk Factors of Abnormally High Cerebral Velocities in Patients with Sickle Cell Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 430-430 ◽  
Author(s):  
Francoise Bernaudin ◽  
Suzanne Verlhac ◽  
Lena Coïc ◽  
Cecile Arnaud ◽  
Annie Kamdem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
G6pd Deficiency ◽  
Intensive Therapy ◽  
Univariate Analysis ◽  
Beta Globin ◽  
Alpha Thalassemia ◽  
Cerebral Mri ◽  
Independent Risk Factors

Abstract Background Predicting the severity of sickle cell anemia (SCA) is important for providing better informed genetic counseling and for better targeting of intensive therapies. Stroke is the most severe complication in children with SCA and is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). We attempted to define the risk factors associated with high velocities. Methods This study concerned the Créteil pediatric SCA cohort, composed of newborn patients, screened and followed at our Center since birth, and of patients secondarily referred to the Center because of the severity of their disease. Time-averaged mean of maximum velocities (TAMMX) higher than 200 cm/sec were considered as abnormal, resulting in initiation of a transfusion program initiated</DEL>. Cerebral MRI/MRA was done after the age of 5 years or earlier in case of abnormal TCD. Alpha </DEL>genes and beta-globin haplotypes were determined. Baseline biological parameters (G6PD activity; WBC, PMN, Reticulocytes, Platelets counts; Hemoglobin, Hematocrit, HbF, LDH levels; MCV; SpO2) were obtained a minimum of 3 months away from a transfusion, one month from a painful episode, after 18 months of age and, before intensive therapy. Results SS children (390; 189 F, 201 M) were annually explored by TCD (n=2286) since 1992, and followed for a total of 1962 patient-years. The follow-up before initiation of intensive therapy was 1032 patient-years. Nineteen patients experienced an overt stroke. TCD was abnormal in 65 of 390 patients (17%). MRI (n=850) was performed in 268 patients, was abnormal in 86 cases and showed silent infarcts in 67 of 249 patients (27%). Silent infarcts were seen in 33% of patients with abnormal TCD. Alpha genes study, available in 336 patients, demonstrated alpha-thalassemia in 158 patients (47%): 31 had a deletion of 2 genes (7.9%) and 127 of 1 gene (32.6%). G6PD deficiency was present in 26 of 228 evaluated patients (11%). Beta-globin haplotypes studied in 316 patients were Car/Car in 125 (40%), Ben/Ben in 76 (24%), Sen/Sen in 30 (9%) and, “other” in 85 (27%). Univariate analysis showed that the risk of abnormally high velocities was not related to sex, beta-globin haplotypes, pain and acute chest syndrom rates, WBC, PMN, platelets counts, HbF level and SpO2 but was significantly associated with the absence of alpha-thalassemia (p< 0.001), G6PD deficiency (p=0.012), low Hb and Ht levels (p< 0.001), high reticulocyte count (p=0.008), high MCV (p=0.004) and high LDH level (p<0.001). Multivariate logistic regression analysis showed that absence of alpha-thalassemia [OR= 14.5, 95% CI (2.6–79.7)], (p=0.002); G6PD deficiency [OR=6.7, 95% CI (1.7–26.1)], (p=0.006) and, LDH > 1200 UI/L [OR=4.5, 95% CI (1.5–13.5)], (p=0.007) were independent risk factors of abnormally high velocities. Conclusion This study confirms that the risk of high velocities in patients with SCA is significantly decreased by the presence of alpha-thalassemia. It shows for the first time that hemolysis is a more significant risk factor than the degree of anemia and that absence of alpha-thalassemia, G6PD deficiency and hemolysis are significant independent risk factors of cerebral vasculopathy in patients with SCA.

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