title: 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 (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
  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.
authors.affiliation: Department of General Surgery, Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, No. 82, Cuiyingmen, Lanzhou, Gansu Province, China, 730030, yingzhenwang@163.com.
authors.forename: Ying-zhen
authors.initials: YZ
authors.lastname: Wang
authors.forename: You-cheng
authors.initials: YC
authors.lastname: Zhang
authors.forename: Jun-sheng
authors.initials: JS
authors.lastname: Cheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Ni
authors.forename: Pei-wu
authors.initials: PW
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Yu-long
authors.initials: YL
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D055371:Acute Lung Injury / Q000378:metabolism*; D000818:Animals; D002108:Ceruletide / Q000737:chemistry*; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D006538:Heptanoic Acids; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D008315:Malondialdehyde; D002108:Ceruletide; D009195:Peroxidase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse