Protective effects of rutin against hemoglobin oxidation.
A prooxidant drug, primaquine (PQ) was used to produce oxidative stress in human red blood cells (RBC) in vitro. Rutin, a plant flavonoid, did not prevent PQ-induced cell lysis but protected against hemoglobin (Hb) oxidation inside RBC. After PQ removal, rutin failed to reduce preformed met-Hb indicating that the rutin protective effect manifests only in the presence of PQ. Since H2O2 was proved to mediate PQ-induced Hb oxidation, authentic Hb was studied for its reaction with H2O2 and rutin in solution. Rutin partially protected oxy-Hb against H2O2-induced oxidation and heme loss. Rutin was also shown to delay H2O2-induced met-Hb oxidation to ferryl-Hb. Rutin directly reduced ferryl-Hb to met-Hb in stoichiometric (1:1) reaction characterized by a rate constant of 100 to 130/M/sec. It is assumed that by reducing ferryl-Hb, rutin prevents oxy-Hb from reacting with ferryl-Hb (comproportionation reaction), thus preventing half of the oxy-Hb molecules from being converted to met-Hb. This mechanism is consistent with 50% inhibition by rutin (at the maximum of its activity) of PQ-induced oxy-Hb oxidation in RBC. The present results demonstrate new antioxidant properties of rutin that may be useful in diminishing oxidative damage to pathological red blood cells.
Grinberg
L N
LN
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Rachmilewitz
E A
EA
Newmark
H
H
D000975:Antioxidants / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008706:Methemoglobin / Q000032:analysis; D010084:Oxidation-Reduction / Q000187:drug effects; D011319:Primaquine / Q000494:pharmacology; D012431:Rutin / Q000494:pharmacology*
D000975:Antioxidants; D006454:Hemoglobins; D012431:Rutin; D008706:Methemoglobin; D011319:Primaquine