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.