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- Title
Protective Effects of BML-111 on Cerulein-Induced Acute Pancreatitis-Associated Lung Injury via Activation of Nrf2/ARE Signaling Pathway.
- Authors
Wang, Ying-zhen; Zhang, You-cheng; Cheng, Jun-sheng; Ni, Qian; Li, Pei-wu; Han, Wei; Zhang, Yu-long
- 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 (50 μg/kg) seven times at hourly intervals and Escherichia coli lipopolysaccharide (10 mg/kg) once after the last dose of cerulein immediately. BML-111 (1 mg/kg) was administered 1 h before the first injection of cerulein. Samples were taken at 3, 6, 12, and 24 h 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 NAD(P)H: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.
- Subjects
CERULEIN; PANCREATITIS; CELLULAR signal transduction; LUNG injuries; NF-kappa B; ANTIOXIDANTS; LIPOPOLYSACCHARIDES
- Publication
Inflammation, 2014, Vol 37, Issue 4, p1120
- ISSN
0360-3997
- Publication type
Article
- DOI
10.1007/s10753-014-9836-y