P55 Endogenous hydrogen sulfide ameliorates secretory phospholipase A2 (sPLA2)-induced acute pancreatitis model in the rat

Abstract

Acute pancreatitis (AP), a painful and inflammatory disease of the pancreas, is one of the most common patient gastrointestinal diseases worldwide, but there is still no effective pharmacological treatment. It is usually associated with high serum concentrations of phospholipase A2 (PLA2). Recently, it has been suggested that the endogenous gasotransmitter hydrogen sulfide (H2S) acts as a mediator of acute pancreatitis. Endogenously, H2S is produced as a metabolite of homocysteine (Hcy) by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). This study aimed to investigate the effects of endogenous H2S in a model of AP in rats. AP was evoked by injection of secretory PLA2 from Crotallus durrisus terrificus (Cdt; 300 mg/kg) snake venom into the common bile duct of rats pretreated with an inhibitor of CSE, propargylglycine (Pgly; 50 mg/kg; i.p., −30 min) or vehicle (0.1 ml). Four hours later, rats were submitted to abdominal nociceptive behavioral test (von Frey) and euthanized. Blood and pancreas were collected and processed to measure plasma amylase, H2S generation and inflammatory parameters (oedema, myeloperoxidase activity) in pancreas. Treatment with PGly markedly reduced inflammation in the pancreas of rats with pancreatitis, but neither increased serum amylase nor abdominal hyperalgesia was affected by this treatment. The kinetics of H2S generation over 60 min in pancreas revealed that CSE and CBS are both expressed in naive pancreas tissue, and a significant difference is seen between control and inflamed pancreas. Inhibition of CSE and CBS reduces H2S generation in pancreas. We conclude that endogenous gaseous messenger molecule H2S plays a functional role in mediating microvascular and cellular changes (oedema and cell influx) in the pancreas, but not the related nociceptive mechanisms of PLA2-induced AP.