Heme breakdown and ischemia/reperfusion injury in grafted liver during             living donor liver transplantation.
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.
Department of Anesthesiology and Resuscitology, Okayama University                     Medical School, Okayama, Japan.
Junya
J
Matsumi
Hiroshi
H
Morimatsu
Takashi
T
Matsusaki
Ryuji
R
Kaku
Hiroko
H
Shimizu
Toru
T
Takahashi
Takahito
T
Yagi
Masaki
M
Matsumi
Kiyoshi
K
Morita
D000293:Adolescent; D000328:Adult; D000818:Animals; D002248:Carbon Monoxide / Q000032:analysis; D045853:Exhalation; D005260:Female; D006418:Heme / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D015427:Reperfusion Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D006418:Heme; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1