Inhibitory effect of trimidox on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages.
We examined the effect of trimidox (3,4,5-trihydroxybenzamidoxime) on the production of nitric oxide (NO) by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages. Trimidox (50 - 300 microM) concentration-dependently inhibited NO production by LPS (0.01, 0.1, or 1 microg/ml) after incubation for 24 h. LPS-induced expression of inducible NO synthase (iNOS) and degradation of IkappaBalpha were prevented by trimidox. The protective effect against NO production by LPS was not only observed in prior incubation but also later incubation with trimidox until iNOS was activated by LPS. These results suggest that trimidox has a predominantly protective effect against LPS-induced production of NO via iNOS expression.
Kanno
Syu-ichi
S
Department of Clinical Pharmacotheraputics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. syu-kan@tohoku-pharm.ac.jp
Kakuta
Mai
M
Kitajima
Yasue
Y
Osanai
Yuu
Y
Kurauchi
Kaori
K
Ohtake
Takaharu
T
Ujibe
Mayuko
M
Uwai
Kouji
K
Takeshita
Mituhiro
M
Ishikawa
Masaaki
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology*; D015153:Blotting, Western; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D013778:Tetrazolium Salts; D013844:Thiazoles
C074761:3,4,5-trihydroxybenzamidoxime; D000199:Actins; D001550:Benzamidines; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013778:Tetrazolium Salts; D013844:Thiazoles; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C022616:thiazolyl blue