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

Abstract

BackgroundThe 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. MethodsWe 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. ResultsModels 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. ConclusionBML-111 could protect against acute injury via regulation RAAS.