The treatment for acute pancreatitis (AP) is still based on supportive care. The search for a new drug is a continuing challenge for many researchers. Rosiglitazone, an oral anti-hyperglycemic agent used for non-insulin-dependent diabetes mellitus, is a high-affinity synthetic agonist for peroxisome proliferator-activated receptor-gamma (PPAR-γ) and was also discovered to have anti-inflammatory effect. This study was carried out to investigate the effect of different doses of rosiglitazone on the development of acute pancreatitis (AP) induced experimentally by L-arginine in albino rats. Sixty-four male rats were divided into four groups: group I (control), group II (rosiglitazone group) subdivided into 3 subgroups (IIa,b,c) and were received different doses of the drug (3,10,50 mg/kg as a single oral dose), group III (AP group) were received single injection of L-arginine (250 mg/100gm b.w., i.p.) and group IV (rosiglitazone pre-treated group) subdivided into 3 subgroups (IVa,b,c) and were administered different doses of the drug (3,10,50 mg/kg as a single oral dose) one hour prior to AP induction. The rats were sacrificed at 24 hours after AP induction, blood samples were collected for assessment of serum amylase, MDA and catalase enzyme activity, in addition, TNF-α and IL-6 were determined in the serum. Pancreatic tissues were also collected for histopathological examination. Our results revealed that rosiglitazone pre-treatment produced dose-dependent attenuation of pancreatic tissue damage as evidenced by reduction of serum amylase and improvement of pancreatic histology. Rosiglitazone pre-treated rats also showed significantly decreased levels of pro-inflammatory cytokines (TNF-α and IL-6) and the lipid peroxidation marker (MDA) while the serum catalase activity was increased in a dose-dependent manner. In the light of these findings, rosiglitazone confers significant dose-dependent protection against L-arginine-induced acute pancreatitis in rats and this beneficial effect is probably due to its anti-inflammatory and anti-oxidant activities. It could represent a new therapeutic target in the treatment of acute pancreatitis. |
