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.