picibanil and Liver-Failure--Acute

We investigated the tolerance of mice to carbon tetrachloride (CCl(4))-induced fulminant hepatic failure (FHF) in mice with daily intraperitoneal (i.p.) injection of high-dose CCl(4) (4 ml/kg). The tolerance was induced by preliminary i.p. administration of a low dose of CCl(4) (1 ml/kg) 24 h prior to the initial high-dose administration of CCl(4) (4 ml/kg). These mice were protected from death because of FHF induced by subsequent daily high-dose injection of CCl(4). This protection appears to result from a priming effect of the innate immune activity of CCl(4). The crude lipid extracted from the liver of low-dose CCl(4) injected mice also protected mice from death because of FHF. Examination of the innate immunological system using OK-432 (picibanil) revealed that the protection results from a priming effect of the innate immune activity with the low-dose CCl(4) or the crude lipid extract.

Topics: Alanine Transaminase; Animals; Calcium; Carbon Tetrachloride; Hepatocytes; Immunity, Innate; Injections, Intraperitoneal; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Mice; Mice, Inbred Strains; Picibanil; Tumor Necrosis Factor-alpha

We studied protective effects of dibutyryl cyclic AMP (DBcAMP 15 mg/kg i.p.) and OK-432 (5 KE/body), and the role of the spleen on D-galactosamine (D-Gal 500 mg/kg i.p.) and lipopolysaccharide (endotoxin: Et 0.5 mg/kg i.p.) induced acute liver failure. The survival rates were 10% in the control group (D-Gal+Et), 53% in the group I A (DBcAMP was administered at 1 hour before D-Gal administration), 79% in the group I B (Splenectomy was performed at 24 hours before D-Gal administration on the group I A), 87% in the group II A (OK-432 was administered at 24 hours before D-Gal administration), and 64% in the group II B (Splenectomy was performed at 24 hours before D-Gal administration on the group II A). GOT activities and TNF activities were significantly improved in the treatment groups, and in the group I B and group II A, they were more improved than in the group I A and group II B. In conclusion, spleen had the positive effect for OK-432 treatment, and also had the negative effect for DBcAMP treatment on acute liver failure induced by D-Gal and Et.

Topics: Animals; Bucladesine; Galactosamine; Lipopolysaccharides; Liver Failure, Acute; Male; Picibanil; Rats; Rats, Wistar; Spleen; Splenectomy