Get access

Melatonin prolongs graft survival of pancreas allotransplants in pigs


Address reprint requests to Joaquín José García, Department of Pharmacology and Physiology, Faculty of Medicine, University of Zaragoza, c) Domingo Miral s/n, E-50009, Zaragoza, Spain.


Abstract:  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 1–7. 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, = 0.013) and the AA group (9.4 ± 1.6 days, = 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-α-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.

Get access to the full text of this article