Induction of specific stress response increases resistance of rat liver allografts to cold ischemia and reperfusion injury.
Heme oxygenase-1 (HO-1) has been shown to increase cellular resistance against oxidative injury, but the functional significance of this is currently obscure. We investigated the protective role of HO-1, induced by tin-protoporphyrin IX (SnPP), in attenuating liver transplantation injury. Lewis rats were intraperitoneally treated with saline as control, 50 micro mol/kg of SnPP, or 2 mg/kg of cycloheximide (CHX) before SnPP injection. Gene expression of HO-1 was induced after either treatment with SnPP- or CHX + SnPP instead of saline, whereas HO-1 protein synthesis was enhanced in Kupffer-like dendritic cells of the SnPP-treated group. Following reperfusion of liver grafts preserved for 30 h, there were fewer intercellular adhesion molecule-1-positive cells in SnPP-treated livers, significantly reduced numbers of dead cells, and enhanced graft viability. The present data suggest that increased synthesis of HO-1 protein by SnPP pre-conditioning is linked to the improved liver graft viability through inhibition of inflammatory adhesion molecules.
Uchida
Yasushi
Y
Research Institute for Artificial Organs, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, 003-0006 Sapporo, Japan.
Tamaki
Tohru
T
Tanaka
Mitsuko
M
Kaizu
Takashi
T
Tsuchihashi
Sei-ichiro
S
Takahashi
Tsuyoshi
T
Kawamura
Akio
A
Kakita
Akira
A
D000818:Animals; D002470:Cell Survival; D015925:Cryopreservation; D003513:Cycloheximide / Q000494:pharmacology; D004198:Disease Susceptibility; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000201:enzymology*; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D008665:Metalloporphyrins; D011524:Protoporphyrins; D018799:Intercellular Adhesion Molecule-1; D003513:Cycloheximide; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1