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Protective Effects of BML-111 on Cerulein-Induced Acute Pancreatitis-Associated Lung Injury via Activation of Nrf2/ARE Signaling Pathway

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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.

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ACKNOWLEDGMENTS

The authors thank Ms. Hong-yan Guo, Ms. Xiao-ni Ma, and Mr. Jie Cheng for excellent technical assistance and Mr. Xi-ping Shen for his help with statistical analysis during this study.

Conflict of Interest

The authors have declared that there is no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, Hepato-Biliary-Pancreatic Institute, Lanzhou University Second Hospital, No. 82, Cuiyingmen, Lanzhou, Gansu Province, China, 730030

    Ying-zhen Wang, You-cheng Zhang, Jun-sheng Cheng, Qian Ni, Wei Han & Yu-long Zhang

  2. Emergency Center, Lanzhou University Second Hospital, No. 82, Cuiyingmen, Lanzhou, Gansu Province, China, 730030

    Ying-zhen Wang & Pei-wu Li

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  1. Ying-zhen Wang
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Correspondence to You-cheng Zhang.

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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 37, 1120–1133 (2014). https://doi.org/10.1007/s10753-014-9836-y

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  • DOI: https://doi.org/10.1007/s10753-014-9836-y

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