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 sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs. Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic water-soluble polymers widely used in biological, chemical, clinical and pharmaceutical settings.
To evaluate the protective effect of a 35-kDa molecular weight PEG (PEG35) on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.
Wistar rats were assigned at random to a control group, a cerulein–induced AP group and a PEG35 treatment group. AP was induced by five hourly intraperitoneal injections of cerulein (50 μg/kg/bw), while the control animals received saline solution. 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 (TNFα), 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 models of in vivo and in vitro pancreatic damage.
Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats. The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas. In contrast, pancreatic tissue mRNA expression of interleukin 10 was markedly increased. PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats. Furthermore, the activation of pro-inflammatory markers and inflammation-induced cell death in pancreatic acinar cells treated with TNFα, cerulein or staurosporine was significantly reduced by PEG35 treatment, in a dose-dependent manner.
PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42J-treated cells through the attenuation of the inflammatory response and associated cell death. PEG35 may be a valuable option in the management of AP.
Core Tip: Acute pancreatitis (AP) is a sudden inflammatory condition of the pancreas with variable involvement of peri-pancreatic tissues and/or remote organ systems. This disease is a major clinical challenge for which no specific pharmacological therapy currently exists. The manuscript describes the protective role of 35-kDa molecular weight polyethylene glycol (PEG35) on cerulein-induced AP. PEG35 treatment was able to lessen the inflammatory process in the pancreas and associated cell death in cerulein-induced AP and in vitro models of pancreatic damage.