Melatonin prolongs graft survival of pancreas allotransplants in pigs

作者：Garcia Gil Francisco A; Albendea Carlos D; Escartin Jorge; Lampreave Fermin; Fuentes Broto Lorena; Rosello Catafau Joan; Lopez Pingarron Laura; Reiter Russel J; Alvarez Alegret Ramiro; Garcia Joaquin J^*

来源：Journal of Pineal Research, 2011, 51(4): 445-453.

DOI：10.1111/j.1600-079X.2011.00908.x

• ascorbic acid
• ischemia-reperfusion
• inter-a-trypsin inhibitor heavy chain 4
• melatonin
• oxidative stress
• pancreas transplantation

Oxidative stress is involved in ischemia-reperfusion injury and allograft rejection after transplantation. We studied two well-known antioxidants, melatonin and ascorbic acid (AA), in relation to the survival of a pancreas transplantation model without immunosuppression. Forty-eight Landrace pigs were divided into three groups (n = 16 each; eight donors and eight recipients) that received melatonin, AA, or no antioxidant therapy (controls). Melatonin and AA were administered (10 mg/kg body weight) intravenously to donors and recipients during surgery and on postoperative days 17. The molecules were also added (5 mm) to a University of Wisconsin preservation solution during organ cold storage. Melatonin significantly delayed acute rejection and prolonged allograft survival (25.1 +/- 7.7 days) compared with the controls (8.1 +/- 0.8 days, P = 0.013) and the AA group (9.4 +/- 1.6 days, P = 0.049). Melatonin reduced indicators of oxidative stress, malondialdehyde, and 4-hydroxyalkenals, in pancreatic samples collected during procurement, cold ischemia, and reperfusion. Melatonin also reduced serum pig-major acute-phase protein/inter-a-trypsin inhibitor heavy chain 4 (pMAP/ITIH4) in the early post-transplantation period. AA only partially reduced oxidative damage 30 min postreperfusion and failed to prevent pMAP/ITIH4 elevations. These findings suggested that melatonin may be a useful therapeutic tool for organ transplantation.

• 出版日期2011-11