Glucosamine inhibits inducible nitric oxide synthesis

Glucosamine is widely used in Europe for treatment of arthritis in humans. Based on recent findings that excess production of nitric oxide (NO) by ind ucible NO synthase (iNOS) mediates the pathogenesis of arthritis, we hypoth esized that glucosamine may inhibit NO synthesis. To test this hypothesis, we used an in vivo rat model of lipopolysaccharide (LPS)-induced inflammati on. Intravenous administration of D-glucosamine (0.5 mmol/kg) 6 h before, a t the time of, and 6 h after intraperitoneal LPS injection (1 mg/kg) decrea sed urinary excretion of nitrate by 31 and 48%, respectively, at days 1 and 2 post LPS administration. When cultured macrophages were treated with LPS (1 mug/ml) to induce iNOS expression, addition of 0.1, 0.5, 1, and 2 mM D- glucosamine decreased NO production by 18, 38, 60, and 89%, respectively. G lucosamine had no effect on cellular arginine, NADPH or tetrahydrobiopterin concentrations, but dose-dependently suppressed iNOS protein expression. S imilar decreases in iNOS protein occurred in spleen, lung, and peritoneal m acrophages of glucosamine-treated rats. These studies demonstrate that gluc osamine is a novel inhibitor of inducible NO synthesis via inhibition of iN OS protein expression, and provide a biochemical basis for the use of gluco samine in treating chronic inflammatory diseases such as arthritis, (C) 200 0 Academic Press.