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Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway.
Inflammation. 2014 Aug; 37(4):1120-33.I

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+Show Affiliations

Department of General Surgery, Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, No. 82, Cuiyingmen, Lanzhou, Gansu Province, China, 730030, yingzhenwang@163.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24550037

Citation

Wang, Ying-zhen, et al. "Protective Effects of BML-111 On Cerulein-induced Acute Pancreatitis-associated Lung Injury Via Activation of Nrf2/ARE Signaling Pathway." Inflammation, vol. 37, no. 4, 2014, pp. 1120-33.
Wang YZ, Zhang YC, Cheng JS, et al. Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway. Inflammation. 2014;37(4):1120-33.
Wang, Y. Z., Zhang, Y. C., Cheng, J. S., Ni, Q., Li, P. W., Han, W., & Zhang, Y. L. (2014). Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway. Inflammation, 37(4), 1120-33. https://doi.org/10.1007/s10753-014-9836-y
Wang YZ, et al. Protective Effects of BML-111 On Cerulein-induced Acute Pancreatitis-associated Lung Injury Via Activation of Nrf2/ARE Signaling Pathway. Inflammation. 2014;37(4):1120-33. PubMed PMID: 24550037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of BML-111 on cerulein-induced acute pancreatitis-associated lung injury via activation of Nrf2/ARE signaling pathway. AU - Wang,Ying-zhen, AU - Zhang,You-cheng, AU - Cheng,Jun-sheng, AU - Ni,Qian, AU - Li,Pei-wu, AU - Han,Wei, AU - Zhang,Yu-long, PY - 2014/2/20/entrez PY - 2014/2/20/pubmed PY - 2015/3/4/medline SP - 1120 EP - 33 JF - Inflammation JO - Inflammation VL - 37 IS - 4 N2 - UNLABELLED: 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. SN - 1573-2576 UR - https://www.unboundmedicine.com/medline/citation/24550037/Protective_effects_of_BML_111_on_cerulein_induced_acute_pancreatitis_associated_lung_injury_via_activation_of_Nrf2/ARE_signaling_pathway_ L2 - https://doi.org/10.1007/s10753-014-9836-y DB - PRIME DP - Unbound Medicine ER -