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

Tsung Ying Chen, Miao Hui Sylvia Lin, Wei Ting Lee, Sheng Yang Huang, Ying Hsin Chen, Ai Chiang Lee, Hsiao Wen Lin, E. Jian Lee

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13 Citations (Scopus)

Abstract

Objective: We explored the putative anti-inflammatory effects of nicotinamide against experimental stroke. Design: Prospective laboratory study. Setting: Research laboratory in a university teaching hospital. Subjects: Adult male Sprague-Dawley rats (250-300 g). Interventions: 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. Measurements and Main Results; 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). Conclusions: Nicotinamide effectively attenuated postischemic nuclear factor-kappa]B activation and exhibited robust anti-inflammatory actions against ischemic stroke.

Original languageEnglish
Pages (from-to)532-537
Number of pages6
JournalCritical care medicine
Volume40
Issue number2
DOIs
Publication statusPublished - 2012 Feb 1

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

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