PROTECTIVE EFFECT OF UKRAIN AGAINST ACUTE ACETAMINOPHEN-INDUCED HEPATITIS IN RATS

LEVINA O.A.1, GONCHAROVA I.A.2, FILATOVA T.G.1, NADEEV A.P.3, NOWICKY W.4, SUKHENKO T.G.5, KOLESNIKOVA O.P.5, KOROLENKO Т.А.1

1)  Laboratory of Cellular Biochemistry, Institute of Physiology, Russian Academy of Medical Sciences, Novosibirsk, Russia.
2)  First Hospital of Municipal Infectious Diseases, Novosibirsk, Russia.
3)  Novosibirsk Medical Academy, Novosibirsk, Russia.
4)  Ukrainian Anti-Cancer Institute, Vienna, Austria.
5)  Institute of Clinical and Experimental Immunology, Russian Academy of Medical Sciences, Novosibirsk, Russia.

Address for correspondence: T.A. Korolenko, Laboratory of Cellular Biochemistry, Institute of Physiology, Russian Academy of Medical Sciences, 4 Timakov Street, Novosibirsk 630117, Russia.

Summary: 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 (GdCI3, 7.5 mg/kg i.v, administered 24 h before AAP), 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 GdCI3 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.