Serum paraoxonase undergoes inhibition and proteolysis during experimental acute pancreatitis

Oxidative stress has a primary role in the pathogenesis of severe acute pancreatitis. Then, the antioxidant capacity is a critical factor in the progression of this disease. Serum paraoxonase-1 (PON1) is an esterase associated with high-density lipoprotein, which clinical interest resides in its ability to prevent or limit the lipid oxidation. The aim of this study was to investigate changes in PON1 activity in the early stages of acute pancreatitis and to find out if its alteration is related with the severity of the disease. To this purpose, we used an experimental model of taurocholate-induced mild and severe acute pancreatitis. Our results showed that serum activity and PON1 concentration decreased 18 h after the induction of a severe acute pancreatitis. In vitro analysis revealed that incubation with oxidized lipids obtained from pancreatitis samples results in the inactivation of the enzyme in a concentration-dependent manner. In addition to oxidative inactivation, we observed by Western blot, an immunoreactive band suggestive of proteolytic degradation of the enzyme, altogether indicating that during severe acute pancreatitis, there is a significant decrease in serum PON1 activity. This decrease is related with inactivation of the enzyme by oxidized lipids, probably followed by proteolytic degradation of the enzyme.