AIM: To investigate if ischemia/reperfusion (I/R) injury in aged liver could be alleviated by heme oxygenase-1 (HO-1). METHODS: Three groups of SD rats (16 mo old) were studied. Group 1: control donors received physiological saline 24 h before their livers were harvested; group 2: donors were pretreated with hemih 24 h before their livers were harvested; and group 3: donors received hemin 24 h before their livers were harvested and zinc protoporphyrin (ZnPP, HO-1 inhibitor) was given to recipients at reperfusion. The harvested livers were stored in University of Wisconsin solution (4℃) for 6 h, and then transplanted to syngeneic rats. Serum glutamic oxaloacetic transaminase (SGOT), apoptotic cells, and apoptotic gene were measured 3, 6, 12, 24, 48 h after reperfusion. We measured the apoptotic index by TUNEL, determined the expression of antiapoptotic Bcl-2 and proapoptotic (caspase-3) gene products by Western blot.. RESULTS: After 3, 6, 12, 24, and 48 h of reperfusion, the SGOT levels (584.4±85.8 u/L, 999.2±125.2 u/L, 423.4±161.3 u/L, 257.8±95.8 u/L, and 122.4±26.4 u/L) in hemin group were significantly (all P<0.05) lower than those in saline group (1082.2±101.2 u/L, 1775.2±328.3 u/L, 840.4±137.8 u/L, 448.6±74.3 u/L, and 306.2±49.3 u/L). Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL+) liver cells 3, 6,12, 24, and 48 h after reperfusion (5.16±0.73, 10.2±0.67, 9.28±0.78, 7.14±1.12, and 4.78±0.65) (P<0.05) could be detected in hemin liver grafts, as compared to controls (7.82±1.05, 15.94±1.82, 11.67±1.59, 8.28±1.09, and 6.36±0.67). We detected the increased levels of Bcl-2 (1.5-fold) expression and compared with saline controls. These differences were most pronounced at 12 h after transplantation. In contrast, an active form of proapoptotic caspase-3 (p20) protein was found to be 2.9-fold lower at 24 h in hemin-pretreated group, as compared to saline liver transplant controls. CONCLUSION: HO-1 overexpression can provide potent protection against cold I/R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism. AIM: To investigate if ischemia / reperfusion (I / R) injury in aged liver could be alleviated by heme oxygenase-1 (HO-1). METHODS: Three groups of SD rats (16 mo ​​old) were studied. Group 1: control donors received physiological saline 24 h before their livers were harvested; group 2: donors were pretreated with hemih 24 h before their livers were harvested; and group 3: donors received hemin 24 h before their livers were harvested and zinc protoporphyrin (ZnPP, HO- 1 inhibitor) was given to recipients at reperfusion. The harvested livers were stored in University of Wisconsin solution (4 ° C) for 6 h, and then transplanted to syngeneic rats. Serum glutamic oxaloacetic transaminase (SGOT), apoptotic cells, and apoptotic gene were We measured the apoptotic index by TUNEL, determined the expression of antiapoptotic Bcl-2 and proapoptotic (caspase-3) gene products by Western blot .. RESULTS: After 3, 6 , 12, 24, and 48 h of reperfusion, the SGOT leve ls (584.4 ± 85.8 u / L, 999.2 ± 125.2 u / L, 423.4 ± 161.3 u / L, 257.8 ± 95.8 u / L, and 122.4 ± 26.4 u / L) in hemin group were significantly (all P <0.05) (1082.2 ± 101.2 u / L, 1775.2 ± 328.3 u / L, 840.4 ± 137.8 u / L, 448.6 ± 74.3 u / L, and 306.2 ± 49.3 u / L). Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL +) liver cells 3, 6, 12, 24 and 48 h after reperfusion (5.16 ± 0.73, 10.2 ± 0.67, 9.28 ± 0.78, 7.14 ± 1.12 , and 4.78 ± 0.65) (P <0.05) could be detected in hemin liver grafts, as compared to controls (7.82 ± 1.05, 15.94 ± 1.82, 11.67 ± 1.59, 8.28 ± 1.09, and 6.36 ± 0.67) Levels of Bcl-2 (1.5-fold) expression and compared with saline controls. These differences were most pronounced at 12 h after transplantation. In contrast, an active form of proapoptotic caspase- 3 (p20) protein was found to be 2.9- fold lower at 24 h in hemin-pretreated group, as com pared to saline livertransplant controls. CONCLUSION: HO-1 overexpression can provide potent protection against cold I / R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism.