Short-Term Effects of Chlorpromazine on Oxidative Stress in Erythrocyte Functionality: Activation of Metabolism and Membrane Perturbation

Thepurpose of this paper is to focus on the short-termeffects of chlorpromazine on erythrocytes because it is reported that the drug,
unstable in plasma butmore stable in erythrocytes, interactswith erythrocytemembranes,membrane lipids, and hemoglobin. There
is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore
the influence of long-termtreatment.We think that evaluating the short-termeffects of the drugmay help to clarify the sequence of
chlorpromazinemolecular targets fromwhich some long-termeffects derive.Our results indicate that although the drug is primarily
intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein
carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of
caspase 3, and, markedly, influences the ATP and reduced glutathione levels, with subsequent exposure of phosphatidylserine at
the erythrocyte surface. Overall our observations on the early stage of chlorpromazine influence on erythrocytes may contribute
to better understanding of new and interesting characteristics of this compound improving knowledge of erythrocyte metabolism.