Iron Metabolism And Oxidative Stress In The Patients With Non-transfusion Dependent Thalassemia

Objective:The aim of this study was to investigate the status of iron overload,iron metabolism,erythropoiesis and oxidative stress in non transfusion dependent thalassemia(NTDT)patients,and to explore the relationship between them.Methods:During October 2014 and December 2016,we chose 242 NTDT outpatients(141 males and 101 females)from the First Affiliated Hospital of Guangxi Medical University,including 174 hemoglobin H disease(Hb H disease)patients and 68 beta thalassemia intermediate(P-TI)patients;and we chose 65 healthy controls(36 males and 29 females)from physical examination center of our hospital.The median age of the NTDT patients was 23(2-63)years old,and the median age of the controls was 27(3-57)years old.Serum hepcidin,erythropoietin(EPO),grow differentiation factor-15(GDF15)and soluble transferrin receptor(STfR)were determined by enzyme-linked immunosorbent assay(ELISA)in all patients and controls;Serum malonaldehyde(MDA),superoxide dismutase(SOD)and vitamin C(VC)were determined using colorimetric method in all patients and controls.We also detected the liver iron concentration(LIC)by magnetic resonance imaging(MRI)in 68 NTDT patients(73 Hb H disease patients and 42?-TI patients);and cardiac T2*were detected in 68 patients(42 Hb H disease patients and 26?-TI patients)by MRI.Results:1.The levels of SF in the ?-TI group was significantly higher than Hb H disease and controls(1252.5 ng/ml vs 447.67 ng/ml vs 141.3 ng/ml,p<0.05);and the LIC in the ?-TI group was significantly higher than Hb H disease(14.8mg/g dw vs 6.4mg/g dw,p<0.05);and there were no significant difference on the Cardiac T2 between the patients of P-TI and Hb H disease(32.84ms vs 30.41ms,p>0.05).2.The serum level of hepcidin were decreased in the NTDT thalassemia,and the the serum level of EPO,GDF15 and STfR was increased,especially in the P-TI patients.The level of hepcidin were significant difference between the three group(controls(126.25ng/ml)vs P-TI group(25.58ng/ml)vs Hb H disease group(9.47ng/ml),p<0.05).There were significant difference of the serum GDF15 and STfR between the three groups(the median level of GDF15 and sTfR:?-TI patients>Hb H disease patients>controls,p<0.05);and the levels of EPO were significantly increased in the P-TI patients and Hb H patients when compared with controls(39.10IU/ml vs 33.66IU/ml vs 5.85IU/ml,p<0.05).3.The level of serum hepcidin was negatively associated with GDF15,EPO and STfR in the NTDT patients(r<0,p<0.05);there were no correlation between hepcidin and SF and LIC in the NTDT patients(p>0.05).However,the level of hepcidin was positively associated with SF and LIC in the Hb H patients(r>0,p<0.05).EPO was negatively associated with Hb(r<0,p<0.05),and positively associated with GDF15 and STfR(r>0,p<0.05)in the NTDT patients.4.The median level of MDA and SOD in the controls were 4.10nmol/L and 61.03U/ml;and the level of MDA and SOD were significantly increased in the Hb H patients and ?-TI patients compared with controls(p<0.05).The serum level of VC in the NTDT patients were decreased,there were significant difference between the three group(controls(9.54?g/ml)>Hb H disease group(8.00?g/ml)>P-TI group(7.45?g/ml),p<0.05).5.The level of MDA in the non-deletion Hb H disease was significantly increased compared with deletion Hb H disease(p<0.05);there were no significant difference on MDA,SOD and VC between ? thalassemia intermediate and Hb E/?thalassemia intermediate(p>0.05).6.MDA was positively associated with SF and LIC in the NTDT patients(r>0,p<0.05).Conclusion:1.Most NTDT patients had liver iron overload,particularly in ?-TI patients;NTDT patients seldom existed cardiac iron overload.2.The serum level of hepcidin was decreased,and the level of EPO,GDF15 and STfR were increased in the NTDT patients,particularly in ?-TI patients.Serum EPO,GDF15 and STfR inhibited the expression of hepcidin,and EPO could stimulate the expression of GDF15 and STfR in the NTDT patients.3.Most NTDT patients existed oxidative stress.The serum levels of MDA and SOD were increased,VC levels decreased in the NTDT patients,particularly in P-TI patients.Iron overload promoted oxidative stress in the NTDT patients,and iron chelation therapy or supplementation of antioxidants may be able to reduce oxidative stress.