title: Oxidative damage and genotoxicity biomarkers in transfused and untransfused thalassemic subjects.
abstract: Chronic anemia and tissue hypoxia increase intestinal iron absorption and mitochondrial impairment in thalassemic patients. Regular blood transfusions improve hemoglobin levels but determine an iron overload that induces reactive oxygen species (ROS) overproduction. The aim of this study was to assess cellular oxidative damage by detection of ROS, lipid peroxidation, 8-oxo-dG, and mitochondrial transmembrane potential (Δψ(m)) in transfused and untransfused thalassemic patients. We have also evaluated genotoxicity by CBMN and comet assay. Our data show that ROS and lipid hydroperoxides are significantly higher in thalassemic patients than in controls, especially in untransfused thalassemia intermedia patients. Moreover, the latter have a significant decrease in Δψ(m) that highlights the energetic failure in hypoxic state and the ROS overproduction in the respiratory chain. 8-OHdG levels are higher in thalassemics than in controls, but do not differ significantly between the two patient groups. Both genotoxicity biomarkers highlight the mutagenic potential of hydroxyl radicals released by iron in the Fenton reaction. Values for percentage of DNA in the comet tail and micronuclei frequency, significantly higher in transfused patients, could also be due to active hepatitis C virus infection and to the many drug treatments. Our biomonitoring study confirms the oxidative damage in patients with thalassemia major and shows an unexpected cellular oxidative damage in untransfused thalassemic patients. In addition to iron overload, the results highlight the important role played by hypoxia-driven mitochondrial ROS overproduction in determining oxidative damage in β-thalassemias.
authors.affiliation: Department of Medical and Surgical Pediatric Sciences, University Hospital of Messina, Messina, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ferro
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.forename: Rosa
authors.initials: R
authors.lastname: Civa
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: La Rosa
authors.forename: Gaetano
authors.initials: G
authors.lastname: Randazzo Papa
authors.forename: Barbara
authors.initials: B
authors.lastname: Baluce
authors.forename: Domenico Giuseppe
authors.initials: DG
authors.lastname: D'Ascola
authors.forename: Basilia
authors.initials: B
authors.lastname: Piraino
authors.forename: Carmelo
authors.initials: C
authors.lastname: Salpietro
authors.forename: Angela
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001803:Blood Transfusion; D015687:Cell Hypoxia; D020552:Comet Assay; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000209:etiology; D015227:Lipid Peroxidation; D008297:Male; D053078:Membrane Potential, Mitochondrial; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000097:blood*; D013789:Thalassemia / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000628:therapy*
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007501:Iron; D003849:Deoxyguanosine