Effect of perioperative antioxidant therapy on suboptimal islet transplantation in rats

Islet transplantation success is limited by the posttransplant inflammatory response, and we are investigating the ability of antioxidants to neutralize this islet damage. We have shown that pyruvate can enhance the engraftment and functionality of a suboptimal islet mass in rats. The present study further investigated the effects of pyruvate, as well as the antioxidants vitamin E and vitamin C. In study A, 350 syngeneic islets were transplanted into the liver of chemically diabetic rats. Antioxidant treatment, or vehicle, was administered during the perioperative period and an intraperitoneal glucose tolerance test (IPGTT) was performed 2 months posttransplant. In study B, 500 syngeneic islets were transplanted under the kidney capsule of chemically diabetic rats. Antioxidant treatment was administered during the perioperative period. Islet-bearing kidney grafts were harvested 24, 48, and 96 hours posttransplant for histological study. Results revealed that pyruvate was the only significantly effective treatment in enhancing the engraftment and functionality of a suboptimal islet mass. Respectively, 56% and 80% of pyruvate-treated rats became normoglycemic after islet transplantation in study A and study B and had a normal insulin response to IPGTT. Histology results from the islet-bearing kidneys were inconclusive as to whether or not pyruvate has an antiapoptotic effect. We conclude that pyruvate, but not vitamin E or vitamin C, aids in the engraftment and functionality of a suboptimal islet mass with as much effectiveness as a full mass in this study. Further investigation into the mechanism of pyruvate protection is still warranted.