The effects of roflumilast on the pancreas and remote organs in a cerulein-induced experimental acute pancreatitis model in rats.

Abstract

Systemic damage in acute pancreatitis (AP) can be characterized by oxidative stress and the release of pro-inflammatory cytokines. Roflumilast has been shown to be a potent anti-inflammatory and antioxidant agent. In the present study, we aimed to investigate the effect of roflumilast in cerulein-induced AP. Thirty-two male rats were divided into four groups: group 1 (sham), group 2 (Roflumilast), group 3 (AP), and group 4 (AP+Roflumilast). AP was induced by injecting 4×75μg/kg of body weight at an interval of 1h. Rats were killed after 12h following the last cerulein administration. AP was confirmed by measuring the serum amylase level and inflammatory features. Morphological changes were observed in the pancreas. Amylase levels were higher in the AP and AP+Roflumilast groups than the sham and Roflumilast groups. The serum levels of TNF-α, IL-1β, and IL-6 increased in the AP group, whereas they decreased in the Roflumilast group. The total oxidant activity (TOA) was higher and the total antioxidant capacity (TAC) was lower in the AP group. The administration of roflumilast decreased the TOA and increased the TAC in comparison with the AP group (p<0.05 for both). Roflumilast significantly decreases oxidative stress and inflammatory mediators in the plasma, pancreas, and lung in cerulein-induced AP rats.