Inhibitory effects of flavonoids on free radical-induced hemolysis and their oxidative effects on hemoglobin.
To investigate the effects of flavonoids on free radical-mediated biological membrane damage and the interaction of flavonoids with heme proteins, we studied the effects of quercetin, its glycosides (rutin and quercetin-3-O-glucoside), morin and (-)epicatechin on the hemolysis of the bovine erythrocytes induced by the hydrophilic free radical initiator, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), and their interaction with hemoglobin. These flavonoids retarded the onset of the hemolysis dose-dependently. The effects of quercetin and other flavonoids were much greater than those of dihydric-phenols studied previously. The inhibitory effects of quercetin and its glycosides were stronger than those of morin and (-)epicatechin. In the absence of AAPH, the relatively hydrophobic flavonoids quercetin and morin induced the oxidation of oxyhemoglobin to methemoglobin. Oxidation by quercetin was especially marked. However, this oxidation did not induce hemolysis. These findings indicate that relatively hydrophobic flavonoids penetrate the cytoplasm of erythrocytes, interact with hemoglobin, and oxidize the heme iron.
Niigata University of Pharmacy and Applied Life Sciences, Faculty of Pharmaceutical Sciences, Niigata, Japan. kitagawa@niigata-pharm.ac.jp
Shuji
S
Kitagawa
Hiromi
H
Sakamoto
Hiromi
H
Tano
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008706:Methemoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D047309:Flavones
D004791:Enzyme Inhibitors; D005419:Flavonoids; D016166:Free Radical Scavengers; D006027:Glycosides; D006454:Hemoglobins; D008706:Methemoglobin; D010108:Oxyhemoglobins; D011794:Quercetin; C008548:morin; D047309:Flavones