Protective effects of dibutyryl cyclic AMP on acute hepatic failure in rats

To study the effect of cyclic AMP on liver dysfunction, dibutyryl cyclic AMP (DBcAMP, 15 mg/kg) was given to rats with acute hepatic failure induced by D-galactosamine (D-Gal; 500 mg/kg) and lipopolysaccharide (i.e., endotoxin) (Et; 0.5 mg/kg). The survival rate was only 7% for rats given D-Gal and Et (control group), while it was 100% for rats given seven doses of DBcAMP, and 53% for rats given two doses. The ALT level was high at 3475 +/- 488 KU in group III, while it was 242 +/- 69 KU in group I, and 376 +/- 49 KU in group II. The hepaplastin test level was decreased at 24 hr in all groups except group I, in which it was high at 55 +/- 11%. The serum tumor necrosis factor (TNF) level was 155 +/- 42 IU/ml in group I, 463 +/- 30 IU/ml in group II, and 1334 +/- 328 IU/ml in group III. The results of the blood biochemistry and liver tissue blood flow studies were better in the DBcAMP-treated groups, and the serum TNF levels were also lower in the treated groups. Histological examination of the liver showed extensive necrosis in the control group, but mild necrosis and inflammatory cell infiltration in the DBcAMP-treated groups. Therefore, treatment with DBcAMP suppressed acute hepatic failure induced by D-Gal and Et, resulting in a significant increase in the survival rate. (C) 1996 Academic Press, Inc.