Protective effects of 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitors on oxidative modification of human low density lipoproteins in vitro
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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
Originalsprache | Englisch |
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Seiten (von - bis) | 615-32 |
Seitenumfang | 18 |
Fachzeitschrift | Clinical hemorheology and microcirculation |
Jahrgang | 61 |
Ausgabenummer | 4 |
Publikationsstatus | Veröffentlicht - 2016 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 84955091396 |
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ORCID | /0000-0002-6932-333X/work/148144973 |
Schlagworte
Schlagwörter
- Animals, Antioxidants, Cyclooxygenase 2 Inhibitors/therapeutic use, Humans, Lipoproteins, LDL/analysis, Male, Oxidation-Reduction, Rats, Rats, Inbred WF, Reactive Oxygen Species