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.

• Authors: Mitsutoshi Kimura, Makiko Watanabe, Naoto Ishibashi, Shingo Yanagida, Masahiko Ogihara
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 643 Issue 2-3 Pg. 267-73 (Sep 25 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20619257 (Publication Type: Comparative Study, Journal Article)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• Retinoids
• Vitamin A
• (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
• Tretinoin
• Aspartate Aminotransferase, Cytoplasmic
• Transaminases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferase, Cytoplasmic (blood)
• Dose-Response Relationship, Drug
• Hepatectomy
• Liver (drug effects, pathology, physiopathology)
• Liver Regeneration (drug effects)
• Male
• Mitosis (drug effects)
• Mitotic Index
• Organ Size (drug effects)
• Random Allocation
• Rats
• Rats, Wistar
• Retinoids (therapeutic use)
• Time Factors
• Transaminases (blood)
• Tretinoin (therapeutic use)
• Vitamin A (therapeutic use)