Membrane effects of trifluoperazine, dibucaine and praziquantel on human erythrocytes

Trifluoperazine (TFP) is a potent antipsychotic agent, dibucaine (DBC) is a local anaesthetic and praziquantel (PZQ) is a highly effective agent again st schistosomiasis. The present work was conducted to (i) investigate the c ytotoxic effects of TFP, DEC and PZQ on human erythrocyte membranes; and (i i) compare the alterations induced by the cationic drugs (TFP and DEC) with those induced by the uncharged compound (PZQ), in an attempt to have a bet ter insight on the pathways of each drug-membrane interaction. The erythroc yte morphological alterations induced by sublytic concentrations of TFP, DE C and PZQ were evaluated by scanning electron microscopy and expressed quan titatively by the morphological index. Haemolysis and release of membrane l ipids (phospholipids and cholesterol) produced by selected concentrations o f TFP, DEC and PZQ, were compared with those resulting from the correspondi ng triple concentrations of each drug. Our results showed that the uncharge d molecule of PZQ induces the same morphological alterations (stomatocytosi s) as the cationic drugs TFP and DEC. Haemolysis was shown to vary with the drug used and to be concentration-dependent, with values similar to 10-fol d more elevated for TFP and DEC than for PZQ, which revealed st maximum of 6% haemolysis for the highest concentration tested. Different concentration -response curves were obtained for lipid elution, although the profiles of cholesterol and phospholipids released were similar for all drugs. Neverthe less, at a fixed rate of 50% haemolysis, TFP induced a similar to 2-fold in crement in the elution of cholesterol when compared with that produced by D EC (P < 0.05). The different effects induced by TFP, DEC and PZQ on erythro cyte morphology, haemolysis and lipid exfoliation are related to the physic al and chemical characteristics of each compound. These results suggest tha t distinct cell membrane interaction pathways lead to drug-specific mechani sms of cytotoxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights rese rved.