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

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.

• Authors: Ying-zhen Wang, You-cheng Zhang, Jun-sheng Cheng, Qian Ni, Pei-wu Li, Wei Han, Yu-long Zhang
• Journal: Inflammation (Inflammation) Vol. 37 Issue 4 Pg. 1120-33 (Aug 2014) ISSN: 1573-2576 [Electronic] United States
• PMID: 24550037 (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

Topics

• 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)