Protection by sinomenine against endotoxin-induced fulminant hepatitis in galactosamine-sensitized mice.
Sinomenine, an epimorphinan alkaloid, was tested for protecting hepatitis induced by lipopolysaccharide (LPS) in galactosamine (GalN)-sensitized mice. Sinomenine protected against the hepatic injuries in the dose range of 10-100 mg/kg in a dose-dependent manner and suppressed the production of tumor necrosis factor (TNF), which appeared in serum earlier than aminotransferases in GalN/LPS-treated mice. Sinomenine significantly suppressed the in vitro production of superoxide anion and hydrogen peroxide in the macrophage cultures stimulated with phorbol 12-myristate acetate. It is discussed that sinomenine prevents GalN/LPS-treated hepatic failure by suppressing TNF production and/or reactive oxygen generation.
Kondo
Y
Y
Pharmaceutical Institute Tohoku University, Sendai, Japan.
Takano
F
F
Yoshida
K
K
Hojo
H
H
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016166:Free Radical Scavengers; D005688:Galactosamine / Q000494:pharmacology*; D006520:Hepatitis, Animal / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009019:Morphinans / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D009019:Morphinans; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C009271:sinomenine; D005688:Galactosamine