5-6-dihydroxy-8-aminoquinoline and Hemolysis

To investigate the anti-hemolytic and anti-membranous lipid peroxidation effects of daphnetin.. The inhibition rates of daphnetin on AQD-induced hemolysis and erythrocytic membranous lipid peroxidation were determined by routine in vitro assay for detecting hemolytic toxicity and by HPLC for detecting membranous lipid peroxidation products.. Daphnetin at a range of 10-80 mumol/L inhibited dose-dependently AQD-induced hemolysis and lipid peroxidation by 33.0%-69.2% and 11.9%-58.2%, respectively.. Daphnetin has anti-hemolytic and anti-erythrocytic membranous lipid peroxidation effects.

Topics: Aminoquinolines; Animals; Antioxidants; Dose-Response Relationship, Drug; Erythrocyte Membrane; Hemolysis; In Vitro Techniques; Lipid Peroxidation; Rabbits; Umbelliferones

The individual effects of two putative metabolites of primaquine (5,6-dihydroxyprimaquine and 5,6-dihydroxy-8-aminoquinoline) on the hexose monophosphate shunt (HMS) and on the ATP-dependent proteolytic system which rapidly degrades oxidized erythrocyte protein were measured in intact red blood cells in vitro from two blood donors. In red cells treated with nitrite (1-40 mM) or phenylhydrazine (0.01-10 mM), proteolytic activity was detected only with concentrations (7.5 mM NaNO2 and 0.25 mM phenylhydrazine) causing greater than 15-fold elevation of HMS activity, and glucose-6-phosphate dehydrogenase (G6PD)-deficient (25% of normal activity) red cell suspensions thus treated showed approximately 30% greater proteolysis. G6PD-normal and deficient red cells treated with the primaquine analogs, however, did not experience proteolysis with concentrations (0.25 mM) in excess of those causing 17-fold elevation of HMS activity. Stimulation of the HMS by the primaquine analogs thus appears unrelated to an erythrotoxic oxidative stress. Methylene blue is known to cause an elevation of HMS activity through direct and diaphorase II-dependent oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) which is independent of injurious oxidative stress. It was found that the putative primaquine metabolites also caused direct and diaphorase II-dependent oxidation of NADPH in dilute hemolysate, thus suggesting that the putative primaquine metabolites have a methylene blue-like redox disposition in red blood cells. Results obtained in this study suggest that the hemolytic toxicity of primaquine may be unrelated to processes which lead to oxidative deterioration of red cell protein.

Topics: Adenosine Triphosphate; Adult; Aminoquinolines; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Hydroxylation; Male; NADPH Dehydrogenase; Nitrites; Pentose Phosphate Pathway; Primaquine