PROTECTIVE EFFECTS OF RUTIN AGAINST HEMOGLOBIN OXIDATION

被引:65
作者
GRINBERG, LN [1 ]
RACHMILEWITZ, EA [1 ]
NEWMARK, H [1 ]
机构
[1] RUTGERS STATE UNIV, COLL PHARM, CANC RES LAB, PISCATAWAY, NJ 08855 USA
关键词
METHEMOGLOBIN; FERRYLHEMOGLOBIN; OXYHEMOGLOBIN; PRIMAQUINE; HYDROGEN PEROXIDE;
D O I
10.1016/0006-2952(94)90040-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:643 / 649
页数:7
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