Reorienting of pramipexole as a promising therapy for acute pancreatitis in a rat model by suppressing TLR4\NF-κB p65\NLRP3 inflammasome signaling

Abstract

Objective: Acute pancreatitis (AP), a disorder of global importance, has a growing incidence and prevalence, particularly in the western world. Its complications include pseudo-cysts and chronic pancreatitis. Pramipexole (PMX), a D2/3 receptor selecting agonist used in Parkinsonism, has reported anti-inflammatory effects lately.
 Purpose: Exploring the potential curative role of PMX in an l-arginine-induced acute pancreatitis rat model besides a possible mechanistic pathway. 
 Methods: Rats were divided randomly into three groups: control, l-arginine, and “l-arginine + PMX”. 7 days after AP induction, rats decapitated and estimated for serum amylase, lipase, glucose, pancreatic inflammatory mediators “toll-like receptor-4, nuclear factor- kappa B p65 ,serum tumor necrosis factor-α, NLRP3 inflammasome, caspase-1, interleukin-1 beta, oxidative biomarkers “malondialdehyde, myeloperoxidase, nitrite/nitrate, reduced glutathione, and the apoptotic marker “caspase-3”, with pancreatic histopathological changes. 
 Results: L-arginine mediated AP proved by elevated serum lipase and amylase, pancreatic inflammatory, oxidative and apoptotic markers with infiltration of inflammatory cells using hematoxylin and eosin stain. PMX improved all these adverse signs of AP greatly. 
 Conclusion: PMX might be considered as an innovative therapy for AP due to its remarkable antioxidant, anti-apoptotic, and anti-inflammatory effects, which are attributed to the suppression of the NLRP3 inflammasome and its downstream inflammatory cytokines.

Gentianine facilitates proliferation and inhibits inflammation and oxidative stress in caerulein-triggered acute pancreatitis cell model

“…Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes are vital molecules in inflammation to induce proinflammatory cytokines, they can affect AP progression through the complex interplay [22,23]. The TLR4/NLRP3 pathway has been verified to be a pivotal pathway in AP progression, and many researchers have paid more attentions in the regulation of this pathway in AP.…”