Protective effect of diminazene attenuates myocardial infarction in rats via increased inflammation and ACE2 activity

Abstract

The present study aimed to investigate whether diminazene attenuates myocardial infarction (MI) in rats. In addition, the present study investigated whether ACE2 signaling was involved in the effects of diminazene on protein function. A rat model of acute myocardial infarction (AMI) was established by occlusion of the left anterior descending coronary artery. The AMI model rats received intraperitoneal injections of diminazene (5 mg/kg/day) for 3 days. Treatment with diminazene significantly inhibited the expression of casein kinase and lactate dehydrogenase, and reduced infarct size in AMI rats. The findings indicated that diminazene significantly reduced the levels of inflammatory factors including tumor necrosis factor‑α and interleukin‑6, suppressed the protein expression of cytochrome c oxidase subunit 2 (COX‑2) and inducible nitric oxide synthase (iNOS), and activated angiotensin‑converting enzyme 2 (ACE2), angiotensin II receptor type 1 (AT1R) and MAS1 proto‑oncogene, G protein‑coupled receptor (MasR) protein expression in AMI model rats. In conclusion, the present study demonstrated that diminazene attenuated AMI in rats via suppression of inflammation, reduction of COX‑2 and iNOS expression, and activation of the ACE2/AT1R/MasR signaling pathway.

Isobaric tags for relative and absolute quantitation‑based proteomics reveals potential novel biomarkers for the early diagnosis of acute myocardial infarction within 3�h

“…Previous studies have examined the connection between COX2 and MI. Chen et al found that diminazene, an antiparasitic drug, significantly reduced the expression of COX2 and the infarct area (40). Kim et al revealed that ischemic preconditioning (IPC) exerted a protective effect on MI and ischemia-reperfusion (I/R) injury, and further genetic analysis revealed that most differentially expressed genes were associated with the generation and transformation of energy.…”

The potential actions of angiotensin‐converting enzyme II (ACE2) activator diminazene aceturate (DIZE) in various diseases

“…In addition, after 4 weeks of DIZE treatment in rats with myocardial infarction, DIZE improved left ventricular contractility and relaxation and prevented right ventricular high systolic pressure, also suggesting that DIZE may play an important role on cardiac dysfunction post‐myocardial infarction . However, during myocardial infarction in rats, a western blot study showed that 3 days of DIZE treatment significantly activates ACE2, AT1R and the MasR protein expression, suggesting the beneficial effect of DIZE on post‐myocardial infarction may be due to the ACE2/AT1R/MasR pathway …”

“…47 However, during myocardial infarction in rats, a western blot study showed that 3 days of DIZE treatment significantly activates ACE2, AT1R and the MasR protein expression, suggesting the beneficial effect of DIZE on post-myocardial infarction may be due to the ACE2/ AT1R/MasR pathway. 48 In addition, in the renal cortex of rats with kidney disease, subcutaneous injection of DIZE (15 mg/kg/d for 2 weeks) is associated with a reduction of cortical ACE activity and an increase in cortical ACE2 activity. 46 Interestingly, diabetic rats using streptozotocin, treatment with DIZE restored ACE2 expression in isolated glomeruli and this was associated with increased expression of AT2R.…”

Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19

“…Treatment of ex vivo hearts by administration of 10 −8 M Ang(1-7) into the bath solution using Langendorff technique re-established the impulse conduction during ischemia-reperfusion and reduced incidence of arrhythmias during IR, possibly due to cardiomyocyte hyperpolarization via the activation of sodium pump [ 89 ]. Activation of ACE2 by diminazene aceturate (DIZE) treatment [ 86 , 90 , 91 , 92 ] led to an improvement of almost all evaluated parameters (however, lacking evidence against amelioration of hypertrophy). These effects were abolished by ACE2 inhibition (“compound 16”) [ 84 , 86 ] or by Mas-receptor antagonist (A779) [ 24 , 88 ].…”