Susceptibility of glucose-6-phosphate dehydrogenase deficient red cells to primaquine enantiomers and two putative metabolites-I: effect on reduced glutathione, methemoglobin content and release of hemoglobin

Abstract

The effects of the primaquine (PQ) enantiomers, (+)PQ and (-)PQ, and two putative metabolites [5-hydroxyprimaquine (5HPQ) and 6-desmethyl-5-hydroxyprimaquine (6D5HPQ)] on methemoglobin (Met Hb) and glutathione content and release of hemoglobin into plasma from glucose-6-phosphate dehydrogenase (G-6-PD) deficient red cells were studied in vitro. The results show that a 1.5 mM concentration of (-)PQ produced a significantly greater increase in Met Hb content and decrease in reduced glutathione (GSH) level than did (+)PQ. However, the release of plasma hemoglobin was greater with (+)PQ than with (-)PQ. The hydroxy derivatives of primaquine, 5HPQ and 6D5HPQ, were significantly more active than PQ. Their individual effects differed; whereas 5HPQ produced significantly greater reduction in GSH compared to 6D5HPQ, the effect of 6D5HPQ on Met Hb content and release of plasma hemoglobin was greater than that of 5HPQ. The qualitative effects of these compounds on normal, heterozygous and hemizygous G-6-PD deficient red cells were similar, but quantitatively the effects were greatest on hemizygous G-6-PD deficient cells and intermediate on heterozygous cells.