Published online Oct 21, 2020. doi: 10.3748/wjg.v26.i39.5970
Peer-review started: July 21, 2020
First decision: August 8, 2020
Revised: August 12, 2020
Accepted: September 12, 2020
Article in press: September 12, 2020
Published online: October 21, 2020
Acute pancreatitis (AP) is a common gastrointestinal condition with an increasing incidence worldwide. The course of the disease ranges from a mild, self-limiting condition to a more severe acute illness with a high morbidity and mortality. Our group has previously demonstrated an anti-inflammatory role for a 35-kDa molecular weight polyethylene glycol (PEG35) in an experimental model of severe necrotizing AP. The therapeutic administration of PEG35 notably alleviated the severity of AP and protected against the associated lung inflammatory response, which is the main contributing factor to early death in patients with this condition.
To date, the treatment of AP continues to be supportive as there are no effective pharmacologic therapies available. Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilic properties combined with a low intrinsic toxicity. In this study, we demonstrated the protective role of PEG35 in a mild form of AP.
To evaluate the effect of PEG35 in experimental models of mild acute pancreatitis in vivo and in vitro.
AP was induced by five hourly intraperitoneal injections of cerulein (50 μg/kg/bw). PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α, staurosporine or cerulein. The severity of AP was determined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated cells. Inflammation-induced cell death was also measured in both in vivo and in vitro models of pancreatic damage through apoptosis and necrosis-related assays.
PEG35 treatment significantly improved pancreatic damage in cerulein-induced AP in rats through reduction on lipase levels and tissue edema. Furthermore, PEG35 ameliorated the inflammatory response and associated cell death in vivo and in vitro, in treated-acinar cells, by lowering inflammatory-related cytokines and iNOS gene expression, levels of apoptotic markers and the activity of lactate dehydrogenase.
PEG35 ameliorated pancreatic damage in cerulein-induced AP and cultured acinar AR42J-treated cells through the attenuation of the inflammatory response and associated cell death.
Our study provided evidence of a protective role of PEG35 in a mild form of AP suggesting that PEG35 may be a valuable option in the management of clinical AP.