| 2413 Inducible Nitric Oxide Synthase Inhibition by Aluminum and Zinc Salts | ||
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M.S. PUTT, K.A. TAYLOR, and E.J. BLUMENTHAL, Indiana University- Purdue University, Fort Wayne, USA The inducible form of nitric oxide synthase (iNOS) plays an important role in inflammatory processes. It is expressed by macrophages and other cells in response to various stimuli (e.g. bacteria) as a defense against pathogens through oxidative toxicity, but chronic local high production of nitric oxide (NO) can contribute to host tissue damage, e.g. gingivitis and periodontitis. NOS inhibitors can act as anti-inflammatory agents in models of both acute and chronic inflammation. Zinc salts are widely used in dentifrices and mouthrinses to help control plaque and gingivitis. Zinc's inhibition of gingivitis is usually attributed to its anti-microbial activity, but some evidence indicates possible anti-inflammatory action. Although largely overlooked, aluminum salts exhibit similar activity to zinc salts. Objective: To investigate if aluminum and zinc salts inhibit the ability of iNOS to catalyze the conversion of arginine to NO and citrulline. Methods: Inhibition of iNOS activity was determined using a radiometric assay. The iNOS activity was measured at room temperature by monitoring conversion of tritiated arginine and cofactors in 50mM Tris-HCl buffer to tritiated citrulline and NO. Following separation of positively charged arginine by binding with cation exchange resin and centrifuging in filter spin cups, citrulline was quantified using a liquid scintillation counter. Aqueous aluminum potassium sulfate and zinc chloride solutions were assayed in triplicate for each experiment, which was validated with 0.1mM aminoguanidine, a known iNOS inhibitor. Results: Activity of iNOS was affected by both Al and Zn in a concentration-dependent manner over a 1-decade range starting at 0.1mM, and was fully inhibited by 1mM solutions. The IC50 values were approximately 0.40mM for Al and 0.35mM for Zn. Conclusion: Aluminum and zinc solutions exhibited dose-dependent inhibition of iNOS activity at concentrations below 1mM. These results suggest that anti-inflammatory properties may contribute to zinc's action against gingivitis in oral care products. | ||
| Seq #243 - Adjunct Treatment 10:15 AM-11:30 AM, Friday, 12 March 2004 Hawaii Convention Center Exhibit Hall 1-2 | ||
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