Poly (ADP-ribose) Polimerase (PARP) Inhibition in Experimental Acute Necrotizing Pancreatitis

Abstract

Purpose: Inhibition of poly (ADP-ribose) polimerase (PARP) is shown to reduce inflammation in several entities. Thus, we designed a study to evaluate the efficacy of benzamide (B), a PARP inhibitor, in an experimental model of acute necrotizing pancreatitis (ANP). Methods: Thirty Sprague-Dawley rats were divided into 3 groups: sham, ANP, ANP+B groups. ANP was induced by infusing of 1 mL/kg of 3% sodium taurocholate into the common biliopancreatic duct. ANP+B group received 100 mg/kg/day benzamide i.p. for a total of 3 days after induction of ANP. The surviving animals were killed at the 4th day and their pancreas was harvested for biochemical, microbiological and histopathological analysis. Blood samples from animals were also obtained. Results: In the ANP group, a clear increase in serum amylase and neopterin levels and tissue oxidative stress indices were present; almost all of these changes were found to be reversed near to their normal values in ANP+B group. Histopathologic injury scores were significantly high in ANP group (p<0.05, ANP vs. sham) which were significantly lower in ANP+B group (p<0.05, ANP+B vs. ANP). Evaluation of bacterial translocation presented significantly less infected sites in ANP+B group than in ANP animals (p<0.01). Conclusion: Our data showed that inhibition of PARP with benzamide reduced the severity, the mortality, bacterial translocation rates and neopterin levels in the experimental ANP model of rats.Figure