Effects of trimetazidine in acute pancreatitis induced by L-arginine

Acute pancreatitis is a disease with high morbidity and mortality. Various theories have been suggested regarding the physiopathology of acute pancreatitis, yet the underlying mechanism is not clearly understood. Oxygen free radicals (OFRs) and basic proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), which play a role in acute pancreatitis and other systemic inflammatory conditions, have been suggested to be responsible for the local tissue damage and multiple organ failure that occur during acute pancreatitis. The OFRs lead to membrane lipid peroxidation, changes in the main components of the cytoplasm and early activation of digestive enzymes of pancreatitis, and they initiate protein damage in acute pancreatitis.1–4 L-arginine is a semi-essential amino acid found in our diet. Numerous animal studies have reported on L-arginine–induced acute pancreatitis. In 1984, Mizunuma and colleagues5 developed a new type of experimental necrotizing pancreatitis by intraperitoneally administering a high dose of L-arginine in rats. The model is highly reproducible and noninvasive and produces dose-dependent acinar necrosis; therefore, it is ideal for studying the pathogenesis of acute pancreatitis. In this study, we used L-arginine to create pancreatitis, similar to the study by Szaboles and colleagues.6 Trimetazidine (2,3,4-trimethoxybenzyl-piperazine dihydrochloride; TMZ), which does not have any direct hemodynamic effects, has an anti-ischemic effect at the cellular level.7–9 This drug has an antioxidant effect by protecting the cell against harmful effects of OFRs that arise during ischemia and inflammation.7–11 By decreasing the inhibition of OFR production and membrane lipid peroxidation, TMZ exerts a protective effect.9–12 On the other hand, TMZ is a chemical agent that also inhibits neutrophil infiltration following ischemia/reperfusion.9,13 The aim of this study was to investigate TMZ effects on acute pancreatitis.