Inhibitory potential of rutin on lipopolysaccharide-induced toxicity and inflammatory response of raw U937 cells and macrophages

Abstract

Rutin is an important flavonoid found in plants with enormous pharmacological activities in various experimental models while lipopolysaccharide is an amphipathic glycolipid with potent inflammatory activity. The protective effect of rutin on lipopolysaccharide-mediated cytotoxity and inflammatory effect on U937 cells and macrophages was investigated. U937 cells were incubated with or without rutin (50 - 200 µM) and later exposed to lipopolysaccharide (5 µg/mL). Cell viability and the production of reactive oxygen species were later analyzed. In the other experiment, the cells were differentially-induced to macrophages and incubated with or without rutin before lipopolysaccharide exposure. The secretion of cytokines and expression of some transcription factors and enzymes were analyzed. It revealed that incubating cells with lipopolysaccharide alone caused significant cell death and production of reactive oxygen species which were reduced when cells were pre-incubated with rutin. Exposure of macrophages to lipopolysaccharide also resulted in significant secretion of both TNF-α and IL-6 which was reduced by rutin. Endotoxin also enhanced the expression of the transcription factors (NF-κB and iNOS) while reduced the expression of the antioxidant enzymes superoxide dismutase and catalase. The lipopolysaccharide-induced alterations in transcription were significantly reduced when macrophages were pre-incubated with rutin. Implications of the findings are discussed.