Nitric oxide production and its contribution to hepatocyte proliferation in normal juvenile rats

Naoto Inukai, Mayuko Uchida, Yoko Miyazaki, Takehito Suzuki, Hiroshi Yoshikawa, Kazuaki Tanaka, Hidetoshi Morita, Tatsuya Takizawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Nitric oxide (NO) has been reported as a key mediator in enhancing hepatocyte proliferation during liver regeneration. Juvenile hepatocytes have a strong ability to proliferate while still in their undifferentiated state but the mechanism of NO production and its contribution to hepatocyte proliferation are not yet fully understood. The present study was designed to investigate NO production in the normal liver and its contribution to hepatocyte proliferation in juvenile rats. Endogenous NO production was evaluated quantitatively using a spin trap followed by electron paramagnetic resonance spectroscopy with the Fe-N, N-diethyldithiocarbamate complex as an NOtrapping reagent in the rat liver. NO production in the liver significantly peaked at 3 weeks after birth, but NO synthase (NOS) 3 expression did not change between 2 to 5 weeks after birth, while NOS 1 and NOS 2 mRNA were not detected. Hepatocyte proliferation, measured by the incorporation of 5-bromo-2'-deoxyuridine into the DNA, was found to decline significantly when endogenous NO production was inhibited by the administration of the NOS inhibitor NG-nitro-L-arginine methyl ester. These findings indicate that endogenous NO production peaked at 3 weeks after birth and hepatocyte proliferation declined significantly when NO production was inhibited. Thus, this study provides a novel insight into the contribution of NO to hepatic growth and liver maturation in juveniles.

Original languageEnglish
Pages (from-to)861-867
Number of pages7
JournalJournal of Veterinary Medical Science
Issue number7
Publication statusPublished - Jul 2010
Externally publishedYes


  • Electron paramagnetic resonance (EPR) spectroscopy
  • Hepatocyte
  • Nitric oxide

ASJC Scopus subject areas

  • veterinary(all)


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