Additive effects of dipyridamole and Trolox in protecting human red cells during photodynamic treatment.
OBJECTIVE
Photodynamic treatment (PDT) of red blood cell (RBC) suspensions has been reported to result in virus inactivation, but also in deterioration of cell quality. Recently, we have demonstrated the potential usefulness of the reactive oxygen species scavenger dipyridamole in selectively protecting RBCs against the harmful side-effects of PDT. Unfortunately, dipyridamole-conferred protection against long-term photohaemolysis was incomplete. In the present study, dipyridamole was applied in combination with Trolox (a hydrophilic vitamin E analogue) in order to augment RBC protection.


METHODS
Leucodepleted RBC suspensions (30% haematocrit) were treated with 1,9-dimethylmethylene blue (DMMB) and red light, and the effect of inclusion of dipyridamole and Trolox was assessed on potassium leakage as well as on short-term and long-term photohaemolysis. Possible interference of the scavenger cocktail with virus inactivation was examined using extracellular pseudorabies virus (PRV).


RESULTS
Treatment of RBC with DMMB and red light resulted in enhanced potassium leakage and both short- and long-term haemolysis. Dipyridamole and Trolox showed additive protective effects against induction of potassium leakage and photohaemolysis, suggesting different protection mechanisms for the two scavengers. Combined inclusion of dipyridamole and Trolox did not interfere with efficacy of PRV inactivation.


CONCLUSIONS
Combined inclusion of dipyridamole and Trolox results in substantially improved selectivity of photodynamic treatment of RBC suspensions.
Besselink
G A J
GA
Department of Transfusion Technology, Sanquin Research at CLB, Amsterdam, The Netherlands.
van Engelenburg
F A C
FA
Ebbing
I G
IG
Hilarius
P M
PM
de Korte
D
D
Verhoeven
A J
AJ
D000975:Antioxidants / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000528:radiation effects; D002839:Chromans / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D011558:Herpesvirus 1, Suid / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008027:Light / Q000009:adverse effects; D008751:Methylene Blue / Q000009:adverse effects / Q000031:analogs & derivatives*; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D011188:Potassium / Q000032:analysis; D014775:Virus Activation / Q000187:drug effects / Q000528:radiation effects
D000975:Antioxidants; D002839:Chromans; D004338:Drug Combinations; C435946:dimethylmethylene blue; D004176:Dipyridamole; D011188:Potassium; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D008751:Methylene Blue