Aminoguanidine prevents concanavalin A-induced hepatitis in mice.
Aminoguanidine is an inhibitor of the inducible form of nitric oxide synthase (iNOS). In the present study, the effect of aminoguanidine on concanavalin A-induced hepatitis was examined. Treatment of mice with concanavalin A (10 mg/kg, i.v.) induced interferon-gamma and iNOS mRNA expression in the liver before the elevation of plasma alanine aminotransferase activity. Immunohistochemical study showed the induction of iNOS protein expression in the area of necrosis. Aminoguanidine (1, 3 and 10 mg/kg, i.p.) inhibited the concanavalin A-induced elevation of alanine aminotransferase activity. Aminoguanidine (10 mg/kg, i.p.) did not inhibit concanavalin A-induced interleukin-2, interferon-gamma, tumor necrosis factor-alpha or iNOS mRNA expression in the liver. The plasma nitrite/nitrate level was elevated at 6 and 24 h after concanavalin A treatment. The elevation of nitrite/nitrate was inhibited by aminoguanidine (10 mg/kg, i.p.). From these results, we conclude that nitric oxide formed by iNOS may be involved in the development of concanavalin A-induced hepatitis.
Okamoto
T
T
Research Laboratories, Nippon Chemiphar Co., Ltd., 1-22 Hikokawato, Saitama 341-0005, Misato, Japan.
Masuda
Y
Y
Kawasaki
T
T
Shinohara
M
M
Matsuzaki
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003208:Concanavalin A / Q000633:toxicity*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006520:Hepatitis, Animal / Q000209:etiology*; D007371:Interferon-gamma / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000410:Alanine Transaminase; C004479:pimagedine