Marked increase in urinary excretion of nitrate and N-nitrosothioproline in the osteogenic disordered syndrome rats, lacking ascorbic acid biosynthesis, by administration of lipopolysaccharide and thioproline.
Urinary excretions of nitrate and N-nitrosothiazolidine-4-carboxylic acid (N-nitrosothioproline; NTPRO) were determined in rats with osteogenic disordered syndrome (ODS, od/od), lacking L-ascorbic acid (ASC) biosynthesis, after i.p. administration of Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) followed by thiazolidine-4-carboxylic acid (thioproline, 20 mg/rat). L-Ascorbic acid-sufficient ODS rats showed the excretion of nitrate and NTPRO at the levels of 20.3 +/- 7.9 mumol/24h and 369 +/- 111 pmol/24 h respectively, whereas the levels of nitrate and NTPRO in ASC-deficient (scorbutic) rats increased to 54.7 +/- 5.6 mumol/24 h (P < 0.01) and 796 +/- 367 pmol/24 h (P < 0.05) respectively. Administration of L-arginine further increased urinary excretion of nitrate and NTPRO while D-arginine showed no effect. NG-Monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS), strongly inhibited endogenous formation of both nitrate and NTPRO. These results indicate that increased excretion of NTPRO in ODS rats stimulated by LPS involves induction of NOS leading to an increase in endogenous formation of reactive nitrogen oxides such as N2O3, a potent nitrosating agent at physiological pH conditions. Increased NOS activities in the plasma and various tissues of ODS rats were observed 5 h after treatment with LPS. The possibility of extragastric N-nitroso compound formation in inflammation sites is discussed.
Tsuda
M
M
National Institute of Health Sciences, Tokyo, Japan.
Kurashima
Y
Y
Kosaka
H
H
Ohshima
H
H
Sugimura
T
T
Esumi
H
H
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001206:Ascorbic Acid Deficiency / Q000652:urine*; D001847:Bone Diseases / Q000652:urine*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009566:Nitrates / Q000652:urine*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D009603:Nitroso Compounds / Q000652:urine*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology* / Q000652:urine*; D053778:Thiazolidines
D008070:Lipopolysaccharides; D009566:Nitrates; D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; D009569:Nitric Oxide; C039001:N-nitrosothioproline; C003438:thiazolidine-4-carboxylic acid; D019001:Nitric Oxide Synthase; D001205:Ascorbic Acid