Protective effect of Ukrain against acute acetaminophen-induced hepatitis in rats

A high dose of acetaminophen (AAP; 1000 mg/kg, single, p.o) administered to rats induced acute liver failure with centrolobular degeneration and necrosis. We studied the role of hepatic macrophages (Kupffer cells) in the modulation of the acetaminophen-induced damage to the liver Ukrain, which is known to possess immunomodulatory characteristics, has been shown to exhibit a positive hepatoprotective effect in human viral hepatitis C, significantly preventing liver cell injury. The selective inhibitor of Kupffer cells, gadolinium chloride (GdCl 3 , 7.5 mg/kg i.v., administered 24 h before MP), and the macrophage stimulator carboxymethylated (1→ 3)-beta-D-glucan (CMG; 25 mg/kg i.p., administered 48 h before AAP), were used to modulate the activity of liver macrophages. It was shown that preliminary administration of Ukrain, CMG or GdCl 3 to rats produced in each case a protective effect, normalizing liver functional tests and reducing damage to the liver The role of tumor necrosis factor (TNF)-alpha secretion in the protective effect of these agents in AAP-induced hepatitis is discussed.