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.