Acetylsalicylic acid--induced hemolysis and its mechanism.
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 K(m) 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."
D000293:Adolescent; D000743:Anemia, Hemolytic / Q000139:chemically induced*; D001241:Aspirin / Q000633:toxicity*; D002648:Child; D004905:Erythrocyte Aging / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D005841:Gentisates / Q000633:toxicity*; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D006801:Humans; D008297:Male
D005841:Gentisates; D005954:Glucosephosphate Dehydrogenase; D001241:Aspirin