title: Enhanced susceptibility of erythrocytes deficient in glucose-6-phosphate dehydrogenase to alloxan/glutathione-induced decrease in red cell deformability.
abstract: It has been hypothesized that enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD) deficient red cells(RBCs) is the underlying mechanism for drug- or chemical-induced hemolytic crises in G6PD-deficiency. To further test this hypothesis, we used an alloxan-glutathione system to mimic oxidative stress and see how oxidative damage might affect RBC deformability. RBC deformability, a major determinant of RBC survival in vivo, was monitored by a laser viscodiffractometer. Under our experimental conditions, GSH alone had very little effect on the deformability of either normal or G6PD-deficient RBCs. In contrast, alloxan alone induced a small but significant decrease in the deformability of either normal or G6PD-deficient RBCs. Interestingly, alloxan and GSH together induced a further decrease in the deformability of either normal or G6PD-deficient RBCs. The decrease in deformability in G6PD-deficient RBCs was much more profound than in normal RBCs. In addition, an alloxan-vitamin C system produced a similar deleterious effect on RBC deformability as that produced by the alloxan-GSH system. Appreciable amount of hydroxyl radicals was generated by both alloxan-GSH and alloxan-vitamin C systems as evidenced by the production of hydroxylated products of salicylate which was used as a radical trap. Moreover, salicylate could ameliorate the deleterious effect of the alloxan system on the deformability of RBCs. Taken together, our results demonstrated that G6PD-deficient RBCs were particularly susceptible to oxidant-induced damage leading to a dramatic decrease in their deformability and thus provided strong support for the hypothesis that enhanced oxidant sensitivity of G6PD-deficient RBCs is the underlying mechanism for accelerated destruction of these RBCs in vivo.
authors.affiliation: Chang Gung College of Medicine & Technology, School of Medical Technology, Tao-yuan, Taiwan.
authors.forename: T Z
authors.initials: TZ
authors.lastname: Liu
authors.forename: T F
authors.initials: TF
authors.lastname: Lin
authors.forename: I J
authors.initials: IJ
authors.lastname: Hung
authors.forename: J S
authors.initials: JS
authors.lastname: Wei
authors.forename: D T
authors.initials: DT
authors.lastname: Chiu
mesh_terms: D000496:Alloxan / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000097:blood; D006900:Hydroxylation; D012459:Salicylates / Q000378:metabolism / Q000494:pharmacology; D020156:Salicylic Acid
chemical_list: D012459:Salicylates; D017665:Hydroxyl Radical; D000496:Alloxan; D005978:Glutathione; D020156:Salicylic Acid; D001205:Ascorbic Acid