Inhibition of poly(ADP-ribose) polymerase attenuates acute kidney injury in sodium taurocholate-induced acute pancreatitis in rats.

OBJECTIVES

The aim of our present study was to investigate the efficacy of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in the development of acute kidney injury in an experimental model of severe acute pancreatitis induced by retrograde infusion of sodium taurocholate into the bile-pancreatic duct.

METHODS

Severity of pancreatitis was evaluated by serum amylase, lipase, tumor necrosis factor α, interleukin-1β, interleukin-6, and histological grading. The following markers of renal dysfunction and injury were measured: serum creatinine level, urea nitrogen level, myeloperoxidase activity, and histology. Activation of PARP, intercellular adhesion molecule-1, and P-selectin protein in the kidney was studied using Western blot analysis.

RESULTS

3-Aminobenzamide attenuated the following: (1) serum amylase, lipase, and renal dysfunction; (2) serum concentrations of proinflammatory cytokines; (3) pancreatic and renal pathological injury; (4) renal myeloperoxidase activity; and (5) activation of PARP, intercellular adhesion molecule-1, and P-selectin in the kidney.

CONCLUSIONS

Our results suggest that PARP activation may contribute to kidney injury and that PARP inhibitors may be beneficial in renal disorders associated with severe acute pancreatitis.