Protective Effects of BML-111 on Cerulein-Induced Acute Pancreatitis-Associated Lung Injury via Activation of Nrf2/ARE Signaling Pathway

Abstract

The aim of this study was to investigate whether BML-111 can exert protective effects on cerulein-induced acute pancreatitis-associated lung injury (APALI) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway. Severe acute pancreatitis (SAP) was established by intraperitoneal injection of cerulein (50μg/kg) seven times at hourly intervals and Escherichia coli lipopolysaccharide (10mg/kg) once after the last dose of cerulein immediately. BML-111 (1mg/kg) was administered 1h before the first injection of cerulein. Samples were taken at 3, 6, 12, and 24h after the last injection. Pathologic lesions of the pancreas and lung tissues as well as the levels of serum amylase were analyzed; Myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and quinone oxidoreductase-1 (NQO1) of lung tissue were determined. The findings revealed that the injuries of pancreas and lung were typically induced by cerulein. The administration of BML-111 reduced the levels of serum amylase, lung MPO, lung MDA, the wet-to-dry weight ratio, and the pathology injury scores of the lung and pancreas, which increased in the SAP group. The expressions of Nrf2, HO-1, NQO1, and activity of SOD in lung tissue increased in the BML-111 group compared with those in the SAP group. This study indicates that BML-111 may play a critical protective role in APALI induced by cerulein. The underlying mechanisms of protective role may be attributable to its antioxidant effects through the activation of Nrf2/ARE pathway.