Parstatin prevents renal injury following ischemia/reperfusion and radiocontrast administration.

BACKGROUND/AIMS Parstatin is a 41-mer peptide formed by proteolytic cleavage on activation of the protease-activated receptor 1. Parstatin was recently found to be cardioprotective against myocardial ischemia/reperfusion (IR) injury. In the present study, it was hypothesized that parstatin would protect the kidneys in acute renal failure. METHODS We investigated the effects of parstatin on the renal dysfunction and injury caused either by renal IR injury or contrast-induced nephropathy (CIN) in two animal models. Renal IR injury was induced in rats by bilateral occlusion of renal arteries and veins for 45 min followed by 4 h of reperfusion, while CIN was induced in rabbits by intravenous injection of the radiocontrast medium Iopromide. RESULTS Treatment with parstatin 15 min before or immediately after renal ischemia attenuated the resulting renal dysfunction as demonstrated by the improved biochemical indicators (serum creatinine and fractional excretion of Na(+)) and scintigraphic analysis. The effect was dose depended and provided evidence for a more prominent protection of tubular than glomerulal function. Histopathological examination of the kidneys revealed severe renal damage, which was significantly suppressed by the parstatin. Similarly, administration of a single dose of parstatin before the induction of CIN significantly protected against the resulting renal dysfunction and histologically evidenced renal tubular injury. CONCLUSION These results suggest that parstatin is able to act as nephroprotective agent and may be useful in enhancing the tolerance of the kidney against renal injury associated with clinical conditions of acute renal failure. Further investigation on the mechanism underlying the nephroprotective properties of parstatin is deemed necessary.