The antioxidant drug dipyridamole spares the vitamin E and thiols in red blood cells after oxidative stress.
OBJECTIVE
To test the antioxidant effect of therapeutic doses of dipyridamole on cellular membranes, human erythrocytes were chosen as an appropriate model to study oxidative stress induced by cumene hydroperoxide because of their high content in heme-Fe(2+).


METHODS
The oxidative stress was induced by incubation with 160 micromoll(-1) cumene hydroperoxide and expressed by three main factors: lipid peroxidation by means of kinetics of decrease in fluorescence emission of the probe incorporated in the cell membranes, vitamin E oxidation and intracellular thiol content. The concentrations of dipyridamole tested (2-20 micromoll(-1)) did not exceed pharmacological doses.


RESULTS
After 7 min of incubation at 25 degrees C with the oxidant and 20 micromoll(-1) dipyridamole thiol content was 50.1%+/-2.6 compared with 31.5%+/-2.4 in the absence of the drug. After 12 min vitamin E content was 88.3%+/-2.3 compared with 64.7%+/-3.4 of untreated cells in the absence of dipyridamole. Dipyridamole added 5 min after the oxidation reaction suppressed the fluorescence decrease for a time proportional to the drug concentration.


CONCLUSIONS
Thus, at clinically realistic doses dipyridamole shows a concentration-dependent antioxidant effect. It protects membranes from oxidation and spares the antioxidant power of erythrocytes.
Kusmic
C
C
Institute of Clinical Physiology, CNR, Via Savi, 8-56126, Pisa, Italy. kusmic@ifc.pi.cnr.it
Picano
E
E
Busceti
C L
CL
Petersen
C
C
Barsacchi
R
R
D000975:Antioxidants / Q000494:pharmacology*; D001555:Benzene Derivatives; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014810:Vitamin E / Q000032:analysis / Q000378:metabolism*
D000975:Antioxidants; D001555:Benzene Derivatives; D013438:Sulfhydryl Compounds; D014810:Vitamin E; D004176:Dipyridamole; C007164:cumene hydroperoxide