title: The role of anaemia in oxidative and genotoxic damage in transfused β-thalassaemic patients.
abstract: OBJECTIVE
  Redox imbalance and genotoxic damage are commonly observed in β thalassaemic patients. The aim of this study was to assess the role of anaemia in oxidative and genotoxic damage in regularly transfused thalassaemic patients, undergoing iron chelation therapy.
  
  
  METHODS
  We studied the relationships of haematological, biochemical and clinical parameters with oxidative (reactive oxygen species and 8-oxo-7,8-dihydro-2'-deoxyguanosine) and genotoxic biomarkers (Comet assay and cytokinesis-block micronucleus test) in blood samples from 105 patients. To reduce the early effect of redox-active iron, samples were collected when pharmacokinetics of the iron chelators ensured their maximum effectiveness. The transfusion regimen, cardiac and hepatic magnetic resonance imaging T2* were evaluated to characterize the patient cohort. Labile plasma iron (LPI) was also assayed.
  
  
  RESULTS
  Haemoglobin level had a significant effect on ROS, %DNA in the tail and micronuclei-micronucleated cell frequency (p < 0.05). Higher Hb values reduced redox imbalance. LPI, detectable in 50.5% of patients, was related to the number of apoptotic and necrotic lymphocytes (p = 0.03), demonstrating the cytotoxic effect of iron.
  
  
  CONCLUSIONS
  The results highlight that an adequate transfusion regimen is essential to limit oxidative and genotoxic damage in β-thalassemic patients undergoing chelation therapy.
  
  
  CONCLUSIONS
  Owing to the higher risk of cancer in the thalassaemic cohorts, specific genotoxicity/oxidative biomarkers should be monitored in order to ameliorate and formulate more personalized disease management.
authors: a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , University Hospital of Messina , Messina , Italy.
authors: Elisa
authors: E
authors: Ferro
authors: b Department of Biomedical and Dental Sciences and Morphofunctional Imaging , University of Messina , Messina , Italy.
authors: Giuseppa
authors: G
authors: Visalli
authors: a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , University Hospital of Messina , Messina , Italy.
authors: Maria Angela
authors: MA
authors: La Rosa
authors: a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , University Hospital of Messina , Messina , Italy.
authors: Rosa
authors: R
authors: Civa
authors: c A.S.P. N.5 , Messina , Italy.
authors: Gaetano Randazzo
authors: GR
authors: Papa
authors: d U.O.C. Centro Microcitemia, Riuniti Hospital , Reggio Calabria , Italy.
authors: Domenico Giuseppe
authors: DG
authors: D'Ascola
authors: e U.O.C. Centro Microcitemia , Sant'Agata Militello , Italy.
authors: Gaetano
authors: G
authors: Roccamo
authors: a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , University Hospital of Messina , Messina , Italy.
authors: Basilia
authors: B
authors: Piraino
authors: a Department of Human Pathology of Adult and Developmental Age 'Gaetano Barresi' , University Hospital of Messina , Messina , Italy.
authors: Carmelo
authors: C
authors: Salpietro
authors: b Department of Biomedical and Dental Sciences and Morphofunctional Imaging , University of Messina , Messina , Italy.
authors: Angela
authors: A
authors: Di Pietro
mesh_terms: D000328:Adult; D000740:Anemia / Q000209:etiology* / Q000628:therapy; D015415:Biomarkers; D001803:Blood Transfusion; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism; D019190:Iron Overload / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D007501:Iron
keywords: Comet assay; Genotoxicity; anaemia; cytokinesis-block micronucleus; iron chelators; iron overload; oxidative damage; transfusion therapy