Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway.

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.
AuthorsYing-zhen Wang, You-cheng Zhang, Jun-sheng Cheng, Qian Ni, Pei-wu Li, Wei Han, Yu-long Zhang
JournalInflammation (Inflammation) Vol. 37 Issue 4 Pg. 1120-33 (Aug 2014) ISSN: 1573-2576 [Electronic] United States
PMID24550037 (Publication Type: Journal Article)
Chemical References
  • 5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester
  • Heptanoic Acids
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Malondialdehyde
  • Ceruletide
  • Peroxidase
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Superoxide Dismutase
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse
  • Acute Disease
  • Acute Lung Injury (metabolism)
  • Animals
  • Ceruletide (chemistry)
  • Disease Models, Animal
  • Heme Oxygenase-1 (metabolism)
  • Heptanoic Acids (pharmacology)
  • Lipopolysaccharides (chemistry)
  • Lung (metabolism)
  • Male
  • Malondialdehyde (metabolism)
  • Membrane Proteins (metabolism)
  • Mice
  • Mice, Inbred BALB C
  • NAD(P)H Dehydrogenase (Quinone) (metabolism)
  • NF-E2-Related Factor 2 (metabolism)
  • Pancreatitis (metabolism, pathology)
  • Peroxidase (metabolism)
  • Response Elements
  • Signal Transduction (drug effects)
  • Superoxide Dismutase (metabolism)

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