title: Nitric oxide metabolites and arginase I levels in β-thalassemic patients: an Egyptian study.
abstract: Stored red blood cells become deficient in nitric oxide that limits their ability to transfer oxygen to tissues that need it. The aims of this study are to assess the endogenous nitric oxide metabolites (NOx) and arginase I levels in transfusion-dependent β-thalassemic patients; to compare these levels in patients transfused with fresh RBCs with patients transfused with old RBCs, β-thalassemic minor patients, and normal control; and to correlate these levels with some clinical variables. Group I was composed of 23 patients with homozygous β-thalassemia on hypertransfusion regimen. They were adequately transfused with fresh RBC. Group II was composed of 17 patients with homozygous β-thalassemia on hypertransfusion regimen. They were adequately transfused with old RBCs. Group III was composed of 30 patients with homozygous β-thalassemia. They were adequately transfused with fresh RBCs. Group IV was composed of 18 patients with homozygous β-thalassemia. They were adequately transfused with old RBCs. Both group III and group IV were supposed to be on hypertransfusion regimen, but they did not follow the regimen. Group V was composed of 21 patients of β-thalassemia minor. Nineteen apparently healthy individuals (HbAA) served as a control group (group VI). In addition to routine laboratory investigations, plasma levels of NOx and serum levels of arginase I were assessed in all subjects. The mean values of plasma NOx were significantly decreased in groups III and IV compared to the other groups. Also, the levels of NOx were significantly decreased in patients who received old RBCs compared to the other groups. There were high serum levels of arginase I in groups III and IV compared to the other groups. There were significant negative correlations between plasma NOx and some hemolytic biochemical markers in groups III and IV. There were significant positive correlations between serum arginase I and some hemolytic biochemical markers in groups III and IV. Also, there was a significant negative correlation between plasma NOx and serum arginase I levels in groups III and IV. In non-adequately transfused patients with β-thalassemia major, inactivation of NO correlates with hemolytic rate and is associated with the erythrocyte release of cell-free hemoglobin, which consumes NO directly, and the simultaneous release of the arginine-metabolizing enzyme arginase, which limits bioavailability of the NO synthase substrate, arginine, during the process of hemolysis. New treatments aimed at improving arginine and NO bioavailability through arginase inhibition, suppression of hemolytic rate, oral arginine supplementation, predonation testing, and transfusion of fresh RBCs or use of NO donors represent potential therapeutic strategies for this common hemolytic disorder.
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Sharkeyia, Egypt.
authors.forename: Samy B M
authors.initials: SB
authors.lastname: El-Hady
authors.forename: Manal H
authors.initials: MH
authors.lastname: Farahat
authors.forename: Maha
authors.initials: M
authors.lastname: Atfy
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Elhady
mesh_terms: D001119:Arginase / Q000097:blood*; D001663:Bilirubin / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004534:Egypt / Q000453:epidemiology; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D017086:beta-Thalassemia / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D005293:Ferritins; D007770:L-Lactate Dehydrogenase; C574619:ARG1 protein, human; D001119:Arginase; D001663:Bilirubin