Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals.
The antioxidant and anti-inflammatory activities of two transition metal complexes of bioflavonoid rutin, Fe(rut)Cl(3) and Cu(rut)Cl(2), were studied. It was found that Cu(rut)Cl(2) was a highly efficient in vitro and ex vivo free radical scavenger that sharply decreased (by 2-30 times compared to the parent rutin): oxygen radical production by xanthine oxidase, rat liver microsomes, and rat peritoneal macrophages; the formation of thiobarbituric acid-reactive products in microsomal lipid peroxidation; and the generation of oxygen radicals by broncho-alveolar cells from bleomycin-treated rats. The copper-rutin complex was also a superior inhibitor of inflammatory and fibrotic processes (characterized by such parameters as macrophage/neutrophil ratio, wet lung weight, total protein content, and hydroxyproline concentration) in the bleomycin-treated rats. The antioxidant activity of Fe(rut)Cl(3) was much lower and in some cases approached that of rutin. Fe(rut)Cl(3) also stimulated to some degree spontaneous oxygen radical production by macrophages. We suggested that the superior antioxidant and anti-inflammatory activity of the copper-rutin complex is a consequence of its acquiring the additional superoxide-dismuting copper center. The inhibitory activity of Fe(rut)Cl(3) was lower, probably due to the partial reduction into Fe(rut)Cl(2) in the presence of biological reductants; however, similarly to the copper-rutin complex, this complex efficiently suppressed lung edema.
Afanas'eva
I B
IB
Vitamin Research Institute, Nauchny pr. 14A, 117820, Moscow, Russia. iafan@aha.ru
Ostrakhovitch
E A
EA
Mikhal'chik
E V
EV
Ibragimova
G A
GA
Korkina
L G
LG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D001761:Bleomycin; D012431:Rutin; D003300:Copper; D007501:Iron; D014969:Xanthine Oxidase