2010•Chineae Journal of Organ TransplantationRequires access

Protective effect of edaravone against hepatic ischemia-reperfusion injry in small-for-size rat liver grafts

Jun Ho Song, Wei Guang Xu, Wei En Fu, Xiang‐nong Li, Xuehao Wang

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Abstract

Objective To investigate the protective effect of edaravone against ischemiareperfusion injury in small-for-size rat liver grafts and its possible mechanisms. Methods 40 % small-for-size rat liver transplantation model was established by using modified two-cuff technique, adult male SD rats were used as donors and recipients, and 16 recipient rats were randomly divided into two groups (8 cases in each group), saline control group (control group) and edaravone treatment group (ED group). In the ED group, 3 mg/kg edaravone was given intravenously via penile vein 30 min before transplantation in the recipients. The same amount of saline was given in the control group at the same time points. Serum hepatic function (AST and ALT) and histopathological changes were analyzed; the contents of MDA and SOD, and hepatic myeloperoxidase (MPO) activity in liver grafts after 6 h were determined; and TNF-α levels at 6th h after reperfusion were measured by using enzyme-linked immunosorbent assay (ELISA method). Results As compared with control group,serum AST and ALT levels were significantly reduced at the 6th h after reperfusion in ED group (AST: 825. 50 5±72. 87 vs 1188. 03 ± 124. 04; ALT. 687. 40 5±72. 21 vs 988. 66 ± 91.07, P<0. 01 ).The content of MDA was lower and SOD level was higher in ED group significantly than in control group (P<0. 01). As compared with control group, hepatic TNF-α levels and MPO activity at the 6th h after reperfusion were significantly decreased in ED group (P<0. 01 ). Histopathological analysis revealed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focal necrosis, significant edema, congestion and inflammatory cell infiltration in periportal area at the 6th h after reperfusion in control group, but minimal liver damage was observed in ED group. Conclusion Edaravone could ameliorate early ischemia-reperfusion injury in small-for-size liver grafts significantly.The protective mechanisms were mediated in part by increasing antioxidant ability, inhibiting lipid peroxidation, and down-regulating inflammatory reaction. Key words: Liver transplantation; Edaravone; Transplants; Reperfusion injury

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Objective To investigate the protective effect of edaravone against ischemiareperfusion injury in small-for-size rat liver grafts and its possible mechanisms. Methods 40 % small-for-size rat liver transplantation model was established by using modified two-cuff technique, adult male SD rats were used as donors and recipients, and 16 recipient rats were randomly divided into two groups (8 cases in each group), saline control group (control group) and edaravone treatment group (ED group). In the ED group, 3 mg/kg edaravone was given intravenously via penile vein 30 min before transplantation in the recipients. The same amount of saline was given in the control group at the same time points. Serum hepatic function (AST and ALT) and histopathological changes were analyzed; the contents of MDA and SOD, and hepatic myeloperoxidase (MPO) activity in liver grafts after 6 h were determined; and TNF-α levels at 6th h after reperfusion were measured by using enzyme-linked immunosorbent assay (ELISA method). Results As compared with control group,serum AST and ALT levels were significantly reduced at the 6th h after reperfusion in ED group (AST: 825. 50 5±72. 87 vs 1188. 03 ± 124. 04; ALT. 687. 40 5±72. 21 vs 988. 66 ± 91.07, P<0. 01 ).The content of MDA was lower and SOD level was higher in ED group significantly than in control group (P<0. 01). As compared with control group, hepatic TNF-α levels and MPO activity at the 6th h after reperfusion were significantly decreased in ED group (P<0. 01 ). Histopathological analysis revealed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focal necrosis, significant edema, congestion and inflammatory cell infiltration in periportal area at the 6th h after reperfusion in control group, but minimal liver damage was observed in ED group. Conclusion Edaravone could ameliorate early ischemia-reperfusion injury in small-for-size liver grafts significantly.The protective mechanisms were mediated in part by increasing antioxidant ability, inhibiting lipid peroxidation, and down-regulating inflammatory reaction. Key words: Liver transplantation; Edaravone; Transplants; Reperfusion injury

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Available abstract

Objective To investigate the protective effect of edaravone against ischemiareperfusion injury in small-for-size rat liver grafts and its possible mechanisms. Methods 40 % small-for-size rat liver transplantation model was established by using modified two-cuff technique, adult male SD rats were used as donors and recipients, and 16 recipient rats were randomly divided into two groups (8 cases in each group), saline control group (control group) and edaravone treatment group (ED group). In the ED group, 3 mg/kg edaravone was given intravenously via penile vein 30 min before transplantation in the recipients. The same amount of saline was given in the control group at the same time points. Serum hepatic function (AST and ALT) and histopathological changes were analyzed; the contents of MDA and SOD, and hepatic myeloperoxidase (MPO) activity in liver grafts after 6 h were determined; and TNF-α levels at 6th h after reperfusion were measured by using enzyme-linked immunosorbent assay (ELISA method). Results As compared with control group,serum AST and ALT levels were significantly reduced at the 6th h after reperfusion in ED group (AST: 825. 50 5±72. 87 vs 1188. 03 ± 124. 04; ALT. 687. 40 5±72. 21 vs 988. 66 ± 91.07, P<0. 01 ).The content of MDA was lower and SOD level was higher in ED group significantly than in control group (P<0. 01). As compared with control group, hepatic TNF-α levels and MPO activity at the 6th h after reperfusion were significantly decreased in ED group (P<0. 01 ). Histopathological analysis revealed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focal necrosis, significant edema, congestion and inflammatory cell infiltration in periportal area at the 6th h after reperfusion in control group, but minimal liver damage was observed in ED group. Conclusion Edaravone could ameliorate early ischemia-reperfusion injury in small-for-size liver grafts significantly.The protective mechanisms were mediated in part by increasing antioxidant ability, inhibiting lipid peroxidation, and down-regulating inflammatory reaction. Key words: Liver transplantation; Edaravone; Transplants; Reperfusion injury

Key concepts: Edaravone, Saline, Myeloperoxidase, Medicine, Liver transplantation, Reperfusion injury, Transplantation, Internal medicine

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