Nicotinamide inhibits nuclear factor-kappa B translocation after transient focal cerebral ischemia.

Abstract

We explored the putative anti-inflammatory effects of nicotinamide against experimental stroke. Prospective laboratory study. Research laboratory in a university teaching hospital. Adult male Sprague-Dawley rats (250-300 g). The antioxidant, radical scavenging, and anti-inflammatory actions of nicotinamide were evaluated using a panel of acellular assays and lipopolysaccharide-stimulated RAW 264.7 and BV2 cells. Animals were subjected to transient middle cerebral artery occlusion for 90 mins. Nicotinamide (500 mg/kg) or vehicle was given intravenously at reperfusion onset. Nicotinamide effectively inhibited nuclear factor-κB translocation and binding activity as well as the production of tumor necrosis factor-α, nitrite/nitrate, and interleukin-6 in the lipopolysaccharide-stimulated RAW 264.7 and BV2 cells (p < .05, respectively) but exhibited weak antioxidant and radical-scavenging actions. Relative to controls, nicotinamide-treated animals had significant reductions in neutrophil and macrophage/activated microglial infiltration in the ischemic brain by 53% and 77% (p < .05, respectively). Additionally, nicotinamide significantly attenuated phosphorylation of nuclear factor-κB's inhibitory protein, nuclear factor-κB translocation and binding activity, and the synthesis of inducible nitric oxide in the ischemic brain (p < .05, respectively). Consequently, nicotinamide effectively reduced brain infarction and improved neurobehavioral outcome by 43% and 50% (p < .05, respectively). Nicotinamide effectively attenuated postischemic nuclear factor-kappa]B activation and exhibited robust anti-inflammatory actions against ischemic stroke.