Antioxidant activity of atrial natriuretic peptide (ANP) in the exocrine pancreas

Abstract

We previously reported that ANP is produced by the exocrine pancreasand that it plays a beneficial role in the outcome of acute pancreatitis(AP). It reduces trypsinogen activation and the inflammatoryresponse and restores glutathione depletion. In the present studywe assessed different parameters of oxidative stress and antioxidantdefenses in Sprague Dawley rats with AP induced by four repetitivecerulein injections (40μg/Kg). Thirty minutes before the firstcerulein injection animals were infused with either saline (control) orANP (1μg/Kg/h) for 60 min. Following euthanasia (60 min after thelast cerulein injection) pancreatic samples were harvested. ANOVAfollowed by a Student Newman Keuls was used for statistical analysis.Results are expressed as the mean±SD and p<0.05 or lesswere considered statistically significant (*). ANP reduced NADPHoxidase activity (U/ug protein) (2180±256 vs. 1410±216**). As ANPincreased Nrf2 nuclear translocation (0.158±0.2 vs. 0.398±0.02*)superoxide dismutase (SOD) and catalase expression were assessedby western blot and qRT-PCR. ANP increased SOD proteinand mRNA expression (0.9±0.08 vs; 1.20±0.11*; 0.63±0.12vs. 2.29±0.19*). Catalase showed no protein or mRNA changes asexpected. Carbonyl content was decreased by ANP (5.60±0.6 vs.3.60±0.9*) and TBARS showed no changes in any experimentalgroup. The oxidized form of coenzyme Q9 (isoform in rodents) wasalso reduced by ANP (477.9±56.9vs. 254.7±86.4*). These resultsfurther support previous findings showing that ANP enhances theantioxidant capacity of the pancreas in AP. Current evidence suggeststhat targeting only oxidative stress would not be sufficient tostop the progression of AP, a pathology characterized by a suddenonset and an unpredictably clinical course. In this sense ANP, whichit is produced in the exocrine pancreas, would be beneficial sinceit not only improves the redox status of the pancreas but also significantlyreduces premature trypsinogen activation and the localinflammatory response.