BACKGROUND: Disturbances of oxidative stress and antioxidant status have been reported in patients with Β-ThM and in a limited number of patients with ThI. OBJECTIVES: To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype. DESIGN: Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused. RESULTS: Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly significant positive correlation with age (p〈0.001) and sTfR. Biomarkers with oxidant activity were also significantly increased in ThI patients compared to controls; significantly higher levels for MDA, NTBI, and GSSG/GSHT were found in severe ThI. The activity of antioxidant enzymes GR, GP and SOD, was significantly significantly reduced in patients, especially in the severe type. Vitamin C was mildly reduced in both types of ThI. CONCLUSIONS: Activity of relevant biomarkers of iron and oxidant-antioxidant homeostasis was significantly increased in untransfused patients with ThI. These changes coincide with the severity of clinical phenotype, genotype and bone marrow erythroid activity evaluated by sTfR levels.
BACKGROUND: Disturbances of oxidative stress and antioxidant status have been reported in patients with Β-ThM and in a limited number of patients with ThI. OBJECTIVES: To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype. DESIGN: Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused. RESULTS: Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly significant positive correlation with age (p〈0.001) and sTfR. Biomarkers with oxidant activity were also significantly increased in ThIpatients compared to controls; significantly higher levels for MDA, NTBI, and GSSG/GSHT were found in severe ThI. The activity of antioxidant enzymes GR, GP and SOD, was significantly significantly reduced in patients, especially in the severe type. Vitamin C was mildly reduced in both types of ThI. CONCLUSIONS: Activity of relevant biomarkers of iron and oxidant-antioxidant homeostasis was significantly increased in untransfused patients with ThI. These changes coincide with the severity of clinical phenotype, genotype and bone marrow erythroid activity evaluated by sTfR levels.
Authors: Mona H El-Tagui; Khaled M Salama; Mohamed H El-Sabbagh; Eman R Youness; Marwa Ragaey; Amina Abdel-Salam Journal: Indian J Hematol Blood Transfus Date: 2018-11-22 Impact factor: 0.900