title: Antiepileptic carbamazepine drug treatment induces alteration of membrane in red blood cells: possible positive effects on metabolism and oxidative stress.
abstract: Carbamazepine (CBZ) is an iminostilbene derivative commonly used for treatment of neuralgic pain and bipolar affective disorders. CBZ blood levels of treated patients are within the range of micromolar concentrations and therefore, significant interactions of this drug with erythrocytes are very likely. Moreover, the lipid domains of the cell membrane are believed to be one of the sites where iminostilbene derivatives exert their effects. The present study aimed to deeply characterize CBZ effects on erythrocytes, in order to identify extra and/or cytosolic cell targets. Our results indicate that erythrocyte morphological changes promoted by the drug, may be triggered by an alteration in band 3 functionality i.e. at the level of anionic flux. In addition, from a metabolic point of view this perturbation could be considered, at least in part, as a beneficial event because it could favour the CO2 elimination. Since lipid peroxidation, superoxide and free radical scavenging activities, caspase 3 activity and hemoglobin (Hb) functionality were not modified within the CBZ treated red blood cell (RBC), band 3 protein (B3) may well be a specific membrane target for CBZ and responsible for CBZ-induced toxic effects in erythrocytes. However some beneficial effects of this drug have been evidenced; among them an increased release of ATP and nitric oxide (NO) derived metabolites from erythrocytes to lumen, leading to an increased NO pool in the vasculature. In conclusion, these results indicate that CBZ, though considered responsible for toxic effects on erythrocytes, can also exhibit effects that at least in some conditions may be seen as beneficial.
authors.affiliation: Department of Chemical Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres 31, 98166 Messina, Italy. sficarra@unime.it
authors.forename: Silvana
authors.initials: S
authors.lastname: Ficarra
authors.forename: Francesco
authors.initials: F
authors.lastname: Misiti
authors.forename: Annamaria
authors.initials: A
authors.lastname: Russo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carelli-Alinovi
authors.forename: Ersilia
authors.initials: E
authors.lastname: Bellocco
authors.forename: Davide
authors.initials: D
authors.lastname: Barreca
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Laganà
authors.forename: Ugo
authors.initials: U
authors.lastname: Leuzzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Toscano
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
authors.forename: Antonio
authors.initials: A
authors.lastname: Galtieri
authors.forename: Ester
authors.initials: E
authors.lastname: Tellone
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D000927:Anticonvulsants / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000927:Anticonvulsants; D002245:Carbon Dioxide; D009569:Nitric Oxide; D002220:Carbamazepine; D000255:Adenosine Triphosphate