4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

Abstract

Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.

4‐Phenylbutyric acid, a potent endoplasmic reticulum stress inhibitor, attenuates the severity of collagen‐induced arthritis in mice via inhibition of proliferation and inflammatory responses of synovial fibroblasts

“…16,17 Many studies implicated ER stress in the pathogenesis of various diseases and demonstrated the therapeutic potential of 4-PBA by using it as a reducer of ER stress. 3,[18][19][20] In the present study, we showed that the expression of ER stress markers was significantly enhanced in IL-1β-stimulated RASFSs, which is consistent with previous reports 9,21 and indicates that ER stress is implicated in the pathogenesis of RA. RASFSs treated with 4-PBA had significantly lower levels of ER stress indicators, which means that 4-PBA reduces ER stress in these cells.…”

Inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid prevents vital organ injury in rat acute pancreatitis

“…Acute pancreatitis (AP) is characterized by local pancreatic inflammation that frequently affects peripancreatic tissues or remote organs and leads to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome, and~20 -30% of all patients progress to severe AP, which has a high mortality rate because of complications (33). Previous study has shown that ERS was involved in AP and associated acinar and ␤-cell injury (11,35), as well as damage of the lung (24). 4-Phenylbutyric acid (4-PBA) has three main pharmacological effects as an ammonia scavenger (14), a weak histone deacetylase inhibitor (16), and an ER stress inhibitor (31).…”

Corrigendum to “4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis”

“…In the article titled “4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis” [ 1 ], the authors made a mistake in the process of analysis by using the recommended concentrations of reference standard which should be diluted by 20 times to be the actual concentrations.…”