AbstractThe hepatoprotective effect of ZNC-2381 (1-(4-aminophenyl) methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b]pyridine-2-one), a novel 2-one dihydroimidazopyridine derivative, has been evaluated in several experimental models of hepatic injury.In mice, oral ZNC-2381, administered at doses of 3, 10 or 30 mg kg−1, 1 h before induction of hepatic injury with concanavalin A, dose-dependently inhibited increases in serum alanine aminotransferase (ALT) activity. Apoptosis of liver cells, as indicated by DNA fragmentation (nucleosome assay) and DNA-ladder formation (electrophoresis), was also inhibited dose-dependently. ZNC-2381 dose-dependently inhibited concanavalin A-induced increases in serum tumour necrosis factor (TNF)-α levels, and TNF-α mRNA expression in the liver. Oral ZNC-2381 also dose-dependently inhibited increases in serum ALT activity in mice with hepatic injury induced by Propionibacterium acnes and a bacterial lipopolysaccharide (LPS) or d-galactosamine-LPS, and in rats with d-galactosamine-induced hepatic injury.These results indicate that oral ZNC-2381 inhibits cytokine (TNF-α) production and cytokine-related hepatocellular apoptosis, and might thus prevent different types of hepatic injury.