Effects and mechanism of the etanercept on pancreatic encephalopathy

Abstract

Pancreatic encephalopathy (Pe) is a common fatal complication of acute pancreatitis (aP). Proinflammatory cytokines such as tumor necrosis factor (TnF)-α and interleukin (il)-6 are generated during aP, and act synergistically to promote Pe and multisystem failure. caerulein-induced aP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TnF-α inhibitor etanercept in Pe models and elucidate the regulatory mechanisms. To model Pe in vitro, rat hippocampal H19-7/iGF-ir neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model Pe in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. at 6 h after administration, it was noted that etanercept downregulated expression of TnF-α, il-1β and il-6 by negatively regulating nF-κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. conversely, etanercept promoted the expression of the neurotrophic and anti-inflammatory hypoxia-inducible factor 1 α . in rat hippocampus, etanercept also reduced the levels of expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein-induced Pe, at least in part via suppression of nF-κB signaling and alleviation of oxidative stress.

Ibuprofen Alleviates Acute Pancreatitis– (AP–) Induced Myocardial Injury by Inhibiting AIM2

“…Acute pancreatitis (AP), an inflammatory condition of the pancreas, destroys the exocrine cells by releasing various pro-inflammatory cytokines that activate the stellate cells. However, the underlying molecular mechanism remains unclear [12]. AR42J are immortalized pancreatic adenocarcinoma cells that share similarities with pancreatic acinar cells.…”

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“…In a rat model etanercept attenuates caerulein-induced pancreatic encephalopathy at least in part via suppression of tumor necrosis factors signaling and mitigation of oxidative stress [7].…”

Changes in noradrenaline and dopamine levels under oxygen debt conditions in the brain of rats during experimental acute pancreatitis

“…The disease affects the stomach, transverse colon, duodenum, and retroperitoneal space. Changes in the pancreas are correlated with systemic changes and damage to many organs, including the brain (pancreatic encephalopathy) (16,23,39). Another classification, the so-called Atlanta classification, which includes the morphological and clinical aspects of AP, is presented in Table 1 (9).…”