Pyruvate in organ transplantation

Abstract

Pyruvate (PY) is a 3-carbon compound present in human tissues and physiologically used by cells as an energetic substrate in anaerobic conditions. In the last few years, we have successfully used PY to protect small bowel (SB), liver, and kidneys from ischemia/reperfusion injury in several experimental models. Although the mechanism of protection is not fully clarified, we have shown increased tissue levels of adenosine driphosphate (ATP) during ischemia. This suggests that providing supra-physiologic concentrations of PY during anaerobic glycolysis might enable the cells to remain viable during prolonged hypoxia. Furthermore, mechanisms such as direct inhibition of oxygen flee radical formation, abrogation of neutrophilic infiltration and reduced up-regulation of adhesion molecules have also been documented in these studies. In light of these findings, we evaluated the efficacy of PY in organ preservation and transplantation. We demonstrated a protective effect on intestinal preservation injury and during acute rejection. Oral PY treatment induced immunologic changes in rejecting allograft, inhibiting perforin and granzyme-b expression and leukocytic infiltration. Protection was also documented on livers after prolonged hypothermic preservation using a PY based preservation solution. Additionally, isolated pancreatic islets were cultured in PY enriched media and maintained viable for up to 120 days followed by in vitro testing and transplantation revealing a well preserved function. All these findings suggest that PY is a potentially beneficial nutrient in patients undergoing organ transplantation and that future clinical application of PY in this field should be encouraged.