Nitric oxide inhibits the formation of advanced glycation end products

Background. Advanced glycation end products (AGEs) are elevated in renal fa ilure and have been implicated in the pathogenesis of several uremic compli cations. Their formation is closely associated with oxidative stress. The r ecent observation that nitric oxide (NO) has an antioxidant effect led us t o examine the possible role of NO in the generation of AGEs. Methods. We examined the effect of NO donors, 2,2'-(hydroxynitrosohydrazono )bis-ethanamine (NOC18) and S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the in vitro formation of pentosidine, which was used as a surrogate marker for AGEs. Bovine serum albumin was incubated under air at 37 degrees C in a medium containing either several AGE precursors or uremic plasma. To eluc idate further the mechanism of the NO effect on AGE formation, we examined the generation of free radicals and carbonyls in pentose-driven pentosidine formation. Results. NO donors significantly inhibit the formation of pentosidine in a dose-dependent manner. The effect is abolished by the addition of a NO scav enging agent, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-o xide (carboxy-PTIO). The inhibitory effect results from NO but not from the NO donor molecule. It is best explained by the ability of NO to scavenge c arbon-centered radicals, hydroxyl radical, and carbonyl compounds. Conclusions. NO inhibits pentosidine formation by scavenging free radicals and by inhibiting carbonyl compound formation. NO might be implicated in th e atherogenic and inflammatory effects of AGEs: Reduced NO production and i ncreased oxidative stress associated with atherosclerotic lesions may accel erate AGE formation and, thus, exacerbate endothelial dysfunction and accel erate the development of atherosclerosis in uremia.