Effects of Febuxostat, a Non-purine Xanthine Oxidase Inhibitor, on Cerulein-induced and L-Arginine-induced Acute Pancreatitis in Rats

Objectives: The effects of xanthine oxidase (XO) inhibitors on acute pancreatitis (AP) have only been reported for allopurinol, with controversial results. We investigated the effects of febuxostat, a potent and selective XO inhibitor, in two AP rat models and compared the results with those of allopurinol. Methods: Using cerulein- and L-arginine-induced AP models, we evaluated the effects of the two XO inhibitors based on histopathological and biochemical parameters, including serum amylase, lipase, blood urea nitrogen, pancreatic malondialdehyde, glutathione peroxidase, reduced-to-total glutathione ratio, and serum/pancreatic XO levels. Results: In cerulein-induced AP, concurrent administration significantly reduced serum and pancreatic XO activities in the Allopurinol (200 mg/kg) and Febuxostat (15 and 30 mg/kg) groups to 2.8%/35.8%, 0.6%/4.9%, and 0.3%/0.7% of controls, respectively ( P <0.05). Therapeutic administration showed similar decreases to 4.9%/56.1% and 0.8%/1.8% of controls ( P <0.05) for Allopurinol (200 mg/kg) and Febuxostat (30 mg/kg), respectively. In L-arginine-induced AP, concurrent allopurinol and febuxostat administration reduces XO activities to 50.8% ( P <0.05)/102.8% and 7.8% ( P <0.01)/78% of controls, respectively. Therapeutic administration produced comparable decreases to 2.7% ( P <0.05)/87.2% and 2.2% ( P <0.05)/70% of controls for Allopurinol (200 mg/kg×2) and Febuxostat (15 mg/kg×2), respectively. These reductions were greater with febuxostat than with allopurinol. Nevertheless, febuxostat and allopurinol failed to alleviate AP. Conclusions: Our results suggest that XO inhibition alone does not have a therapeutic effect on AP and XO is not significantly involved in the progression of AP in either AP model.