Carbon monoxide as a guardian against hepatobiliary dysfunction

Makoto Suematsu, Kosuke Tsukada, Toshihide Tajima, Takehiro Yamamoto, Daigo Ochiai, Hiroshi Watanabe, Yasunori Yoshimura, Nobuhito Goda

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Carbon monoxide (CO) generated through the reaction of heme oxygenase (HO) has attracted great interest in regulation of hepatobiliary homeostasis. The gas generated by HO-2 in the hepatic parenchyma can modestly activate soluble guanylate cyclase (sGC) expressed in hepatic stellate cells in a paracrine manner and thereby constitutively relax sinusoids. Kupffer cells express HO-1, the inducible isozyme, even under normal unstimulated conditions and constitutes approximately 30% of the total HO activity in this organ. Upon exposure to a variety of stressors such as cytokines, endotoxin, hypoxia and oxidative stress, the liver induces HO-1 and overproduces CO. The stress-inducible CO has been shown to guarantee ample blood supply during detoxification of heme and thus to play a protective role in the liver. However, molecular mechanisms by which CO serves as a protectant for hepatocytes, the cells expressing little sGC, remain to be solved. Previous observation suggested that CO modulates intracellular calcium mobilization through inhibiting cytochrome P-450 activities and thereby maintain stroke volume of bile canalicular contraction in cultured hepatocytes. CO also stimulates mrp2-dependent excretion of bilirubin-IXα and helps heme catabolism. Although a direct molecular target responsible for the latter event remains unknown, such properties of CO could support xenobiotic metabolism through its actions on sinusoidal hemodynamics and hepatobiliary systems.

Original languageEnglish
Pages (from-to)134S-139S
JournalAlcoholism: Clinical and Experimental Research
Issue number11 SUPPL.
Publication statusPublished - 2005 Nov


  • Carbon monoxide
  • Gas Biology
  • Heme Oxygenase
  • Metabolome
  • Soluble Guanylate Cyclase
  • Xenobiotic Metabolism

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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