Susceptibility of glucose-6-phosphate dehydrogenase deficient red cells to primaquine, primaquine enantiomers, and its two putative metabolites. II. Effect on red blood cell membrane, lipid peroxidation, MC-540 staining, and scanning electron microscopic studies.
The effects of primaquine (PQ), its enantiomers [(+)PQ,(-)PQ] and hydroxy metabolites [5-hydroxyprimaquine (5HPQ) and 6-desmethyl-5-hydroxyprimaquine (6D5HPQ)] on cell membranes of glucose-6-phosphate dehydrogenase (G-6-PD) deficient red cells were studied in vitro. There was no significant effect of PQ on the malonyldialdehyde (MDA) content of normal and heterozygous red cells, but it caused a significant increase in MDA in G-6-PD deficient red cells (P less than 0.05). There was no noticeable difference between the effects of the two enantiomers on this variable (P greater than 0.05). Compared to PQ, the hydroxy metabolites produced a significantly greater increase in MDA in all the groups studied (P less than 0.001). Of the two hydroxy metabolites, 6D5HPQ was more toxic than 5HPQ. Staining with MC540 showed that exposure to PQ, its enantiomers and two putative metabolites produced significant fluorescence, indicating that the drug produces marked alterations in membrane fluidity. Although the fluorescence was seen both in normal and heterozygous cells, the effect was marked in hemizygous deficient red cells (P less than 0.001). Scanning electron microscopic (SEM) studies revealed that PQ enantiomers had a stomatocytic effect on red cells of normal, heterozygous and hemizygous G-6-PD deficient red cells, whereas the putative metabolites had an echinocytic effect. The effects were most pronounced in G-6-PD deficient red cells.
Agarwal
S
S
Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Gupta
U R
UR
Daniel
C S
CS
Gupta
R C
RC
Anand
N
N
Agarwal
S S
SS
D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008560:Membrane Fluidity / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D011319:Primaquine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D011744:Pyrimidinones; D013237:Stereoisomerism
D011744:Pyrimidinones; C003954:merocyanine dye; D011319:Primaquine