Protective effects of 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitors on oxidative modification of human low density lipoproteins in vitro
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
It has been suggested that 2,3-diaryl-substituted indole-based cyclooxygenase-2 (COX-2) inhibitors (2,3-diaryl-indole coxibs) do not only appear as potent anti-inflammatory agents but also show the ability to scavenge reactive oxygen species (ROS). This led to the hypothesis that 2,3-diaryl-indole coxibs also may act as potent inhibitors of oxidative modification of low-density lipoprotein (LDL), which is considered a key factor in atherogenesis. The aim of this study was to explore i) the reactivity of a series of new synthesized 2,3-diaryl-indoles with several well characterized LDL oxidation systems and ii) subsequent effects on an inflammatory/atherogenic microenvironment. The results demonstrate that under the present experimental conditions 2,3-diaryl-indoles showed potent ROS scavenging activity and were able to markedly inhibit LDL oxidation. Subsequently, this led to a substantial decrease of modified LDL uptake by scavenger receptors in THP-1 macrophages in vitro and in rats in vivo. Moreover, modified LDL-mediated monocyte/neutrophil adhesion to endothelial cells, macrophage NFκB activation, as well as macrophage and endothelial cell cytokine release was diminished in vitro. The reduction of modified LDL-induced atherogenic effects by antioxidant 2,3-diaryl-indole coxibs may widen the therapeutic window of COX-2 targeted treatment.
Details
Original language | English |
---|---|
Pages (from-to) | 615-32 |
Number of pages | 18 |
Journal | Clinical hemorheology and microcirculation |
Volume | 61 |
Issue number | 4 |
Publication status | Published - 2016 |
Peer-reviewed | Yes |
External IDs
Scopus | 84955091396 |
---|---|
ORCID | /0000-0002-6932-333X/work/148144973 |
Keywords
Keywords
- Animals, Antioxidants, Cyclooxygenase 2 Inhibitors/therapeutic use, Humans, Lipoproteins, LDL/analysis, Male, Oxidation-Reduction, Rats, Rats, Inbred WF, Reactive Oxygen Species