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

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.

• Authors: Jia Yu, Wenhong Deng, Weixing Wang, Youming Ding, Hao Jin, Chen Chen, Xiaoyan Chen, Xingcheng Xiong, Sheng Xu
• Journal: Pancreas (Pancreas) Vol. 41 Issue 8 Pg. 1299-305 (Nov 2012) ISSN: 1536-4828 [Electronic] United States
• PMID: 22750969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Acute Kidney Injury (blood, drug therapy, enzymology, pathology, 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, drug therapy, enzymology)
• Peroxidase (analysis)
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (analysis)
• Rats
• Rats, Wistar
• Severity of Illness Index
• Taurocholic Acid (pharmacology)