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Research Article Free access | 10.1172/JCI106349
Department of Pediatrics, University of Wisconsin, School of Medicine, Madison, Wisconsin 53706
Department of Medicine, University of Wisconsin, School of Medicine, Madison, Wisconsin 53706
Find articles by Shahidi, N. in: JCI | PubMed | Google Scholar
Department of Pediatrics, University of Wisconsin, School of Medicine, Madison, Wisconsin 53706
Department of Medicine, University of Wisconsin, School of Medicine, Madison, Wisconsin 53706
Find articles by Westring, D. in: JCI | PubMed | Google Scholar
Published July 1, 1970 - More info
Acetylsalicylic acid (ASA) is known to cause severe hemolytic anemia in some glucose-6-phosphate-dehydrogenase-deficient (G-6-PD-deficient) individuals. To study its mechanism, erythrocytes from an ASA-sensitive patient were transfused into a normal compatible recipient. The administration of 2,5-dihydroxybenzoic (gentisic) acid, a known ASA metabolite with redox properties, to the recipient resulted in a marked decrease in the survival of the patient's erythrocytes. Similar studies with red cells from individuals with A- and Mediterranean variants of G-6-PD revealed no alteration in the erythrocytes' survival. Further studies disclosed that both salicylate and gentisate competitively inhibited the G-6-PD from the ASA-sensitive patient resulting in a marked change in the Km for NADP. These drugs also inhibited the A- and Mediterranean variants of G-6-PD. The magnitude of inhibition, however, was comparatively small and not different from that observed with a normal enzyme.
The above studies suggested that enzyme inhibition by salicylate and gentisate may play an important role in ASA-induced hemolysis. Such an inhibition would further curtail NADPH regeneration, rendering the cells more vulnerable to oxidants. In this connection, gentisate seems to play a major role in ASA-induced hemolysis for it is both a G-6-PD inhibitor and an “oxidant.”