Induction of specific stress response increases resistance of rat liver allografts to cold ischemia and reperfusion injury

• DOI: 10.1111/j.1432-2277.2003.tb00320.x
• Publication Date: 2005-03-11T11:04:08Z
• Authors: Yasushi Uchida; Tohru Tamaki; Mitsuko Tanaka; Takashi Kaizu; Sei-ichiro Tsuchi...; Tsuyoshi Takahashi; Akio Kawamura; Akira Kakita
• Keywords: Male; 0301 basic medicine; Cell Survival; Metalloporphyrins; Gene Expression; Protoporphyrins; 03 medical and health sciences; Animals; Cycloheximide; Cryopreservation; 0303 health sciences; Drug Synergism; Intercellular Adhesion Molecule-1; Immunohistochemistry; Liver Transplantation; Rats; 3. Good health; Liver; Rats, Inbred Lew; Enzyme Induction; Heme Oxygenase (Decyclizing); Reperfusion; Disease Susceptibility; Heme Oxygenase-1

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.