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

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.

• Authors: 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
• Journal: Critical care medicine (Crit Care Med) Vol. 40 Issue 2 Pg. 532-7 (Feb 2012) ISSN: 1530-0293 [Electronic] United States
• PMID: 21926578 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Niacinamide
• Peroxidase

Topics

• Animals
• Behavior, Animal
• Confidence Intervals
• Disease Models, Animal
• Electrophoresis, Gel, Two-Dimensional
• Immunoblotting
• Immunohistochemistry
• Interleukin-6 (analysis, metabolism)
• Ischemic Attack, Transient (drug therapy, metabolism, pathology)
• Lipid Peroxidation (physiology)
• Male
• NF-kappa B (drug effects, metabolism)
• Niacinamide (pharmacology)
• Peroxidase (analysis, metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reference Values
• Statistics, Nonparametric
• Tumor Necrosis Factor-alpha (analysis, metabolism)