Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation

Junya Matsumi, Hiroshi Morimatsu, Takashi Matsusaki, Ryuji Kaku, Hiroko Shimizu, Toru Takahashi, Takahito Yagi, Masaki Matsumi, Kiyoshi Morita

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3 Citations (Scopus)

Abstract

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXα. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-1 gene expression by polymerase chain reaction and HO-1 localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-1 gene expression levels significantly increased after I/R. In addition, HO-1 levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-1 gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-1 gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage.

Original languageEnglish
Pages (from-to)135-140
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Keywords

  • Heme oxygenase
  • Ischemia/reperfusion injury
  • Liver damage
  • Living donor liver transplantation

ASJC Scopus subject areas

  • Genetics

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