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 studies. It was found that Cu(rut)Cl-2 was 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 bronchoalveolar cells from bleomycin-treated rats. The copper-rutin complex wa 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. (C) 2001 Elsevier Science Inc. All rights reserved.