Inhibition of 5-lipoxygenase represses neutrophils activation and activates apoptosis in pancreatic tissues during acute necrotizing pancreatitis

Pancreatic glandular necrosis is rapid inflammation of the pancreas and contributes to severe acute pancreatitis in humans. The pathogenesis of pancreatic tissue inflammation during acute pancreatitis is still largely unknown. Recent studies suggest that 5-lipoxygenase (5-LOX) is an essential mediator in modulating cell death pathways in human diseases. In this study, we aimed to evaluate the effects of a 5-LOX inhibitor, zileuton, on tissue apoptosis and neutrophils activation in pancreatic tissues during acute necrotizing pancreatitis (ANP) in a rat model. In this present study, both mRNA and protein levels of 5-LOX are upregulated during ANP and zileuton treatment is shown to repress ANP-induced upregulation of 5-LOX levels. In addition, zileuton treatment is found to repress blood biomarkers of neutrophils activation such as soluble intercellular adhesive molecular 1 (ICAM-1), soluble E-selectin (E-selectin), soluble P-selectin (P-selectin), leukotriene B4 (LTB4), and myeloperoxidase (MPO). Also, zileuton treatment attenuates pancreatic tissue pathology, upregulates caspase-3, downregulates B-cell lymphoma 2 (Bcl-2), and activates tissue apoptosis evaluated by TUNEL staining. Our results show that 5-LOX plays an important role in activating apoptosis and repressing neutrophils activation during ANP. The current study suggests that 5-LOX can be used as a potential target for the treatment of ANP.