Melatonin prolongs graft survival of pancreas allotransplants in pigs
Article first published online: 1 JUL 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 51, Issue 4, pages 445–453, November 2011
How to Cite
García-Gil, F. A., Albendea, C. D., Escartín, J., Lampreave, F., Fuentes-Broto, L., Roselló-Catafau, J., López-Pingarrón, L., Reiter, R. J., Alvarez-Alegret, R. and García, J. J. (2011), Melatonin prolongs graft survival of pancreas allotransplants in pigs. Journal of Pineal Research, 51: 445–453. doi: 10.1111/j.1600-079X.2011.00908.x
- Issue published online: 19 OCT 2011
- Article first published online: 1 JUL 2011
- Accepted manuscript online: 26 MAY 2011 11:29AM EST
- Received March 28, 2011; Accepted May 24, 2011.
- ascorbic acid;
- inter-α-trypsin inhibitor heavy chain 4;
- oxidative stress;
- pancreas transplantation
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/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.