BML-111, a lipoxin receptor agonist, protects against acute injury via regulating the renin angiotensin-aldosterone system

• Published in: Prostaglandins & other lipid mediators 2019-02, Vol.140, p.9-17
• Main Authors: Chen, Qiong-Feng, Hao, Hua, Kuang, Xiao-Dong, Hu, Quan-Dong, Huang, Yong-Hong, Zhou, Xiao-Yan
• Format: Article
• Language: English
• Subjects: Angiotensin I - metabolism; Angiotensin II - metabolism; Animals; Cytoprotection - drug effects; Down-Regulation - drug effects; Heptanoic Acids - pharmacology; Inflammation; Lipoxins; Liver - drug effects; Liver - injuries; Liver - metabolism; Liver - pathology; Lung Injury - metabolism; Lung Injury - pathology; Lung Injury - prevention & control; Peptide Fragments - metabolism; Peptidyl-Dipeptidase A - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - metabolism; Receptors, Lipoxin - agonists; Renin angiotensin-aldosterone system; Renin-Angiotensin System - drug effects; Up-Regulation - drug effects
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2018.11.001

•Both LXs and RAAS could regulate inflammatory response, oxidative stress, fibrosis, besides proliferation and apoptosis. It seemed the biological effects of renin angiotensin-aldosterone system (RAAS) and Lipoxins (LXs) are similar. The roles of RAAS in chronic disease is more apparent, and we had reported that BML-111(a lipoxin receptor agonist) equilibrated ACE-AngII-AT1R and ACE2-Ang-(1–7)-Mas axis to protect chronic disease hepatic fibrosis in rats. But its role in acute injury is less studied.•In this paper, acute models were used to observe the relations of RAAS and LXs in acute liver/lung injury. The results demonstrated that BML-111 could improve acute liver/lung through regulating RAAS.•BML-111 can protect not only chronic disease but also acute injury via regulating RAAS.RAAS might be novel and potential targets for LXs/analogs against acute and chronic diseases. The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1–7) (Ang-1–7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1–7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. BML-111 could protect against acute injury via regulation RAAS.