Manganese Porphyrin Protects Neonatal Pig Islets against Oxidative Stress and Enhances their Function in Diabetic Mice

Abstract

Significant numbers of pancreatic islets are lost during isolation and early transplantation period due to oxidative stress. Neonatal pig islets are being considered to overcome the shortage of human donors. Manganese (III) tetrakis (N-ethylpyridium-2-yl) porphyrin (MnP) is a synthetic antioxidants that was shown to protect human and murine islets from oxidative stress. We report that pre-treatment of neonatal pig islets with MnP resulted in up-regulation of gene expression of antioxidant enzymes such as superoxide dismutase and antiapoptotic molecules such as survivin. We found that MnP is not toxic to neonatal pig islets. Further, MnP provided protection to neonatal pig islets against H2O2 induced damage. In addition, NSG mice that received islets pre-treated with 34 μM MnP achieved normoglycemia earlier and had significantly lower average blood glucose level compared to other groups. We report that MnP could be beneficial to neonatal pig islets provided protection against oxidative stress and enhanced their function in vivo.