Nitric oxide inhibits the formation of advanced glycation end products.
BACKGROUND
Advanced glycation end products (AGEs) are elevated in renal failure and have been implicated in the pathogenesis of several uremic complications. Their formation is closely associated with oxidative stress. The recent observation that nitric oxide (NO) has an antioxidant effect led us to 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 elucidate 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 scavenging agent, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazoline-1-oxyl 3-oxide (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 carbon-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 the atherogenic and inflammatory effects of AGEs: Reduced NO production and increased oxidative stress associated with atherosclerotic lesions may accelerate AGE formation and, thus, exacerbate endothelial dysfunction and accelerate the development of atherosclerosis in uremia.
Asahi
K
K
Institute of Medical Sciences and Department of Internal Medicine, and Department of Physiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Ichimori
K
K
Nakazawa
H
H
Izuhara
Y
Y
Inagi
R
R
Watanabe
T
T
Miyata
T
T
Kurokawa
K
K
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D002254:Carbonates / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000096:biosynthesis*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012266:Ribose / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology; D014511:Uremia / Q000378:metabolism
D002254:Carbonates; D003432:Cross-Linking Reagents; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C110881:S-nitro-N-acetylpenicillamine; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D012266:Ribose; D001120:Arginine; C062187:pentosidine; D010396:Penicillamine; D008239:Lysine