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.