Article open access publication

Selenium-containing indolyl compounds: Kinetics of reaction with inflammation-associated oxidants and protective effect against oxidation of extracellular matrix proteins

Free Radical Biology and Medicine, Elsevier, ISSN 0891-5849

Volume 113, 2017

DOI:10.1016/j.freeradbiomed.2017.10.344, Dimensions: pub.1092293509, PMID: 29055824,

Affiliations

Organisations

  1. (1) Federal University of Pelotas, grid.411221.5
  2. (2) Adam Mickiewicz University in Poznań, grid.5633.3
  3. (3) University of Copenhagen, grid.5254.6, KU

Countries

Brazil

Denmark

Poland

Continents

South America

Europe

Description

Activated white blood cells generate multiple oxidants in response to invading pathogens. Thus, hypochlorous acid (HOCl) is generated via the reaction of myeloperoxidase (from neutrophils and monocytes) with hydrogen peroxide, and peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent is formed from superoxide radicals and nitric oxide, generated by stimulated macrophages. Excessive or misplaced production of these oxidants has been linked to multiple human pathologies, including cardiovascular disease. Atherosclerosis is characterized by chronic inflammation and the presence of oxidized materials, including extracellular matrix (ECM) proteins, within the artery wall. Here we investigated the potential of selenium-containing indoles to afford protection against these oxidants, by determining rate constants (k) for their reaction, and quantifying the extent of damage on isolated ECM proteins and ECM generated by human coronary artery endothelial cells (HCAECs). The novel selenocompounds examined react with HOCl with k 0.2-1.0 × 108M-1s-1, and ONOOH with k 4.5-8.6 - × 105M-1s-1. Reaction with H2O2 is considerably slower (k < 0.25M-1s-1). The selenocompound 2-phenyl-3-(phenylselanyl)imidazo[1,2-a]pyridine provided protection to human serum albumin (HSA) against HOCl-mediated damage (as assessed by SDS-PAGE) and damage to isolated matrix proteins induced by ONOOH, with a concomitant decrease in the levels of the biomarker 3-nitrotyrosine. Structural damage and generation of 3-nitroTyr on HCAEC-ECM were also reduced. These data demonstrate that the novel selenium-containing compounds show high reactivity with oxidants and may modulate oxidative and nitrosative damage at sites of inflammation, contributing to a reduction in tissue dysfunction and atherogenesis.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Danish Open Access Indicator

2017: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2017: Level 1

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 17

Field Citation Ratio (FCR): 3.45

Relative Citation ratio (RCR): 1.04

Open Access Info

Hybrid