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

Pancreas. 2012 Nov;41(8):1299-305. doi: 10.1097/MPA.0b013e318252dbc3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / enzymology
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology
  • Amylases / blood
  • Animals
  • Benzamides / therapeutic use*
  • Blood Urea Nitrogen
  • Cholagogues and Choleretics / adverse effects*
  • Creatinine / blood
  • Enzyme Inhibitors / therapeutic use*
  • Interleukin-6 / blood
  • Male
  • P-Selectin / analysis
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / enzymology
  • Peroxidase / analysis
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / analysis
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Taurocholic Acid / pharmacology

Substances

  • Benzamides
  • Cholagogues and Choleretics
  • Enzyme Inhibitors
  • Interleukin-6
  • P-Selectin
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Taurocholic Acid
  • 3-aminobenzamide
  • Creatinine
  • Peroxidase
  • Poly(ADP-ribose) Polymerases
  • Amylases