Inhibition of heme oxygenase ameliorates sepsis-induced liver dysfunction in rats

Hajime Iwasashi, Masanori Suzuki, Michiaki Unno, Tetsuyuki Utiyama, Masaya Oikawa, Noriko Kondo, Seiki Matsuno

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19 Citations (Scopus)

Abstract

Purpose. The disintegration of heme produces carbon monoxide (CO), a known vasodilator, which is catalyzed by heme oxygenase (HO). This study aimed to clarify the effect of HO inhibition on septicrat livers using two types of HO inhibitors; Sn-protoporphyrin (Sn-PP) and Zn-protoporphyrin (Zn-PP). Methods. Sepsis was induced in male Sprague-Dawley rats by cecal ligation and puncture (CLP). Either NaOH or HO inhibitors were injected intraperitoneally; first 18h prior to CLP, then immediately after CLP. The animals were killed 12 and 24 h after CLP and the liver tissue and plasma were harvested. Results. Using Northern blotting, we found that mRNA of the stress-inducible isozyme, HO-1, was dramatically induced 12 h after CLP. Administering the HO inhibitors, Sn-PP and Zn-PP (5 μmol/kg), induced a significant inhibition of the elevation of aspartate aminotransferase plasma levels, the elevation of cyclic guanosine monophosphete (cGMP) in the liver tissue, and the increase in the sinusoidal space ratio, 24 h after CLP. Both Sn-PP and Zn-PP decreased the mortality rate 24 h after CLP compared with normal saline. Conclusions. CO produced by excessively induced HO-1 after CLP promotes an immoderate dilation of the sinusoidal space through the up-regulation of cGMP, resulting in liver dysfunction. Therefore, administering HO inhibitors at appropriate doses could be beneficial for the amelioration of sepsis-induced liver dysfunction.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalSurgery today
Volume33
Issue number1
DOIs
Publication statusPublished - 2003 Mar 1

Keywords

  • Carbon monoxide
  • Heme oxygenase-1
  • Sepsis
  • Sinusoid

ASJC Scopus subject areas

  • Surgery

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    Iwasashi, H., Suzuki, M., Unno, M., Utiyama, T., Oikawa, M., Kondo, N., & Matsuno, S. (2003). Inhibition of heme oxygenase ameliorates sepsis-induced liver dysfunction in rats. Surgery today, 33(1), 30-38. https://doi.org/10.1007/s005950300005