Protection from D-galactosamine-induced liver injury by orally active novel peptide leukotriene receptor antagonist, ONO-1078

Abstract

Effects of ONO-1078, a novel orally effective peptide leukotriene receptor antagonist specific for leukotrienes C 4 and D 4, on d-galactosamine-induced liver injury were investigated in male Wistar rats. ONO-1078, when given via gastric tubes 1 h before or 2 h after intraperitoneal administration of d-galactosamine, significantly reduced plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 24 h and 48 h after d-galactosamine administration. Similar effect of ONO-1078 was also observed when administered intraperitoneally 30 min before d-galactosamine administration. This protective effect of oral administration of ONO-1078 showed similar dose-dependency between 1 and 90 mg/kg body weight as already reported on guinea-pig asthma models. These results suggest that leukotrienes C 4 and D 4 may play an important role in the early phase of d-galactosamine-induced liver injury.