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.