Next Article in Journal
Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer
Next Article in Special Issue
The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms
Previous Article in Journal
Horizontal Combination of MEK and PI3K/mTOR Inhibition in BRAF Mutant Tumor Cells with or without Concomitant PI3K Pathway Mutations
Previous Article in Special Issue
The Role of Thiocyanate in Modulating Myeloperoxidase Activity during Disease
Open AccessArticle

Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats

1
Discipline of Pathology, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney 2006 NSW, Australia
2
Heart Research Institute, Sydney Medical School, The University of Sydney, Sydney 2006 NSW, Australia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7650; https://doi.org/10.3390/ijms21207650
Received: 31 August 2020 / Revised: 9 October 2020 / Accepted: 12 October 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Role for the Enzyme Myeloperoxidase to Elicit Pathologies)
Reperfusion therapy increases survival post-acute myocardial infarction (AMI) while also stimulating secondary oxidant production and immune cell infiltration. Neutrophils accumulate within infarcted myocardium within 24 h post-AMI and release myeloperoxidase (MPO) that catalyses hypochlorous acid (HOCl) production while increasing oxidative stress and inflammation, thereby enhancing ventricular remodelling. Nitroxides inhibit MPO-mediated HOCl production, potentially ameliorating neutrophil-mediated damage. Aim: Assess the cardioprotective ability of nitroxide 4-methoxyTEMPO (4MetT) within the setting of AMI. Methods: Male Wistar rats were separated into 3 groups: SHAM, AMI/R, and AMI/R + 4MetT (15 mg/kg at surgery via oral gavage) and subjected to left descending coronary artery ligation for 30 min to generate an AMI, followed by reperfusion. One cohort of rats were sacrificed at 24 h post-reperfusion and another 28 days post-surgery (with 4MetT (15 mg/kg) administration twice daily). Results: 3-chlorotyrosine, a HOCl-specific damage marker, decreased within the heart of animals in the AMI/R + 4-MetT group 24 h post-AMI, indicating the drug inhibited MPO activity; however, there was no evident difference in either infarct size or myocardial scar size between the groups. Concurrently, MPO, NfκB, TNFα, and the oxidation marker malondialdehyde increased within the hearts, with 4-MetT only demonstrating a trend in decreasing MPO and TNF levels. Notably, 4MetT provided a significant improvement in cardiac function 28 days post-AMI, as assessed by echocardiography, indicating potential for 4-MetT as a treatment option, although the precise mechanism of action of the compound remains unclear. View Full-Text
Keywords: heart attack; neutrophil; host damage; cardiac damage heart attack; neutrophil; host damage; cardiac damage
Show Figures

Graphical abstract

MDPI and ACS Style

El Kazzi, M.; Shi, H.; Vuong, S.; Wang, X.; Chami, B.; Liu, Y.; Rayner, B.S.; Witting, P.K. Nitroxides Mitigate Neutrophil-Mediated Damage to the Myocardium after Experimental Myocardial Infarction in Rats. Int. J. Mol. Sci. 2020, 21, 7650.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop