Carvedilol attenuates l-arginine induced acute pancreatitis in rats through modulation of oxidative stress and inflammatory mediators.

Acute pancreatitis (AP) is a sudden pancreatic inflammation accompanied by an excessive reactive oxygen species production that provokes inflammation. The present study investigated whether carvedilol can protect against l-arginine induced AP in a rat model and studied the mechanisms associated with its protection. Rats were divided into four groups: a control group, an AP group (injected with 2 doses of l-arginine 250 mg/100 g body weight at 1 h interval, intraperitoneally) on the 22nd day of the experiment, a carvedilol group (10 mg/kg, orally) for 21 successive days, and finally a carvedilol + AP group. It was found that pretreatment with carvedilol decreased α-amylase and lipase activities as well as C-reactive protein (CRP) and malondialdehyde levels; on the other hand, it improved the reduced glutathione (GSH) level and catalase (CAT) activity. In addition, carvedilol markedly decreased all of the following biomarkers: nuclear factor kappa B (NF-κB p65), p38 mitogen-activated protein kinases (P38-MAPK), signal transducer and activator of transcription 1 (STAT1-α), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), and phospholipase A2 (PLA2) levels that was induced by l-arginine. Finally, carvedilol noticeably down regulated the pancreatitis associated protein (PAP2) and the pancreas platelets activating factor (PAF) genes expression. In conclusion: carvedilol protected against l-arginine induced AP in rats, via the inhibition of cellular oxidative stress and inflammatory pathways that contributed to pancreas injury.