Effect of bilirubin on toxicity induced by trifluoperazine, dibucaine and praziquantel to erythrocytes.
Unconjugated bilirubin (UCB), like trifluoperazine (TFP), dibucaine (DBC) and praziquantel (PZQ), induces erythrocyte morphological changes, lysis and lipid exfoliation. In the present study we determined whether TFP, DBC and PZQ toxicity to erythrocytes was potentiated or reverted by UCB. Human erythrocytes were either treated or non-treated with 34.2 micromol/L UCB for 10 min prior to the incubation with toxic concentrations of TFP (0.12 mmol/L), DBC (1.5 mmol/L) or PZQ (3.0 mmol/L), for 1 h (37 degrees C). Studies of toxic effects included morphological analysis of erythrocytes, evaluation of hemoglobin release and loss of membrane lipids. Although UCB has an echinocytogenic effect, its co-incubation with TFP or PZQ did not alter the stomatocytogenic effect of the drug but enhanced DBC-induced stomatocytosis. Cell fusion was a common feature in experiments with DBC. Injurious effect of DBC to erythrocytes was potentiated by UCB as manifested by a marked increase in hemolysis (171%, p<0.05), and in elution of membrane cholesterol (73%, p<0.01) and phospholipids (123%, p<0.01). In opposite, toxic events produced by TFP and PZQ to erythrocytes were not aggravated by UCB. Interestingly, UCB prevented the loss of membrane cholesterol by PZQ (-36%, p<0.01), as well as that of phospholipids by TFP (-28%, p<0.05). These findings indicate that UCB potentiates DBC injury to erythrocytes, while protects membrane lipid elution by PZQ and TFP. Therefore, the relation of the benefits and risks of the administration of DBC to jaundiced patients should be carefully considered.
Brito
M A
MA
Centro de Patogénese Molecular, Faculdade de Farmácia, University of Lisbon, Portugal.
Malheiros
S V
SV
Meirelles
N C
NC
Brites
D
D
D000328:Adult; D001663:Bilirubin / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003992:Dibucaine / Q000633:toxicity*; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011223:Praziquantel / Q000633:toxicity*; D014268:Trifluoperazine / Q000633:toxicity*
D006454:Hemoglobins; D008563:Membrane Lipids; D010743:Phospholipids; D014268:Trifluoperazine; D011223:Praziquantel; D002784:Cholesterol; D003992:Dibucaine; D001663:Bilirubin