Acyclic retinoid NIK-333 accelerates liver regeneration and lowers serum transaminase activities in 70% partially hepatectomized rats, in vivo

Abstract

The effect of an acyclic synthetic retinoid analogue NIK-333, on the restoration of liver mass and recovery of liver function after 70% partial hepatectomy, was compared with natural retinoids in rats in vivo. NIK-333 (0.4 mg/kg/day, p.o.)- and all- trans-retinoic acid (ATRA: 4 mg/kg/day, p.o.)-treated rats showed an approximately 1.3- and 1.2-fold increase in liver-to-body weight ratio, respectively, compared to solvent-administered control rats on day 3 after 70% partial hepatectomy. Accordingly, 5-bromo-2'-deoxyuridine (BrdU)-labeling index in the regenerating liver was significantly higher in NIK-333- and ATRA-treated rats compared with control rats on days 0.5 and 1. However, retinol (40 mg/kg/day, p.o.) did not significantly increase either the liver-to-body weight ratio or the BrdU labeling index. In control rats, liver-related serum transaminase activities such as alanine aminotransferase and aspartate aminotransferase, were rapidly elevated on day 1 and then decreased to near pre-operative levels on day 5 following 70% partial hepatectomy. NIK-333 significantly lowered serum transaminases on days 1 and 3 after 70% partial hepatectomy compared with solvent-administered control rats. The transaminase-lowering effect of NIK-333 was more effective than that of ATRA. Retinol did not significantly decrease serum transaminases compared with the control. These results demonstrate that of the three retinoids, NIK-333 was the most potent in promoting the regeneration of liver mass and function with full recovery after 70% partial hepatectomy.