title: Melatonin prolongs graft survival of pancreas allotransplants in pigs.
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, 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-α-trypsin inhibitor heavy chain 4 (pMAP/ITIH(4)) in the early post-transplantation period. AA only partially reduced oxidative damage 30 min postreperfusion and failed to prevent pMAP/ITIH(4) elevations. These findings suggested that melatonin may be a useful therapeutic tool for organ transplantation.
authors: Department of Surgery, University of Zaragoza, Zaragoza, Spain.
authors: Francisco A
authors: FA
authors: García-Gil
authors: Carlos D
authors: CD
authors: Albendea
authors: Jorge
authors: J
authors: Escartín
authors: Fermin
authors: F
authors: Lampreave
authors: Lorena
authors: L
authors: Fuentes-Broto
authors: Joan
authors: J
authors: Roselló-Catafau
authors: Laura
authors: L
authors: López-Pingarrón
authors: Russel J
authors: RJ
authors: Reiter
authors: Ramiro
authors: R
authors: Alvarez-Alegret
authors: Joaquín J
authors: JJ
authors: García
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D008550:Melatonin / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D016035:Pancreas Transplantation / Q000379:methods*; D013552:Swine; D014184:Transplantation, Homologous
chemical_list: D000510:Alpha-Globulins; D000975:Antioxidants; C011877:inter-alpha-inhibitor; D008550:Melatonin; D001205:Ascorbic Acid