Therapy for acute pancreatitis with platelet-activating factor receptor antagonists

Abstract

Acute pancreatitis (AP) causes release of plateletactivating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAFRAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

“…PAF has also played a role in several other inflammation-related chronic diseases and their related comorbidities, including types I and type II diabetes mellitus [ 212 , 213 , 214 ], acute pancreatitis [ 215 , 216 ], liver injury [ 217 ], inflammation-related intestine tissue dysfunction such as necrotising enterocolitis [ 218 , 219 ], inflammatory ocular diseases [ 220 ], vascular dysfunction during acute lung injury [ 221 ], and autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and Crohn’s disease [ 222 , 223 , 224 ].…”

“…Several PAF inhibitors have been used in these inflammation-related diseases with promising results [ 137 , 216 , 217 , 222 , 225 , 226 ]. These effects were mostly due to the deterioration of PAF-related chronic inflammatory manifestations present in these disorders.…”

Drug discovery and formulation development for acute pancreatitis

“…Abnormal hemorheology also promoted the development of acute pancreatitis from edema to necrotizing. Platelet-activating factor receptor antagonists (PAF-RAs) was found to significantly reduce local and systemic pathogenesis in acute pancreatitis (Chen et al., 2008 ). The early microcirculation disorder of the pancreas can directly or indirectly damage the pancreas, resulting in ischemia injury as well as inflammatory reactions.…”

Advances in researches on the immune dysregulation and therapy of severe acute pancreatitis

“…In contrast, the neutrophils isolated from SAP patients could induce more severe endothelial tissue injury in an ET-independent manner. In the present studies, the platelet-activating factor (PAF) has been considered as a key mediator in the progression of SAP, which can lead to severe complications and high mortality rate (Chen et al, 2008).…”