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Head-to-Head Comparison of Selected Extra- and Intracellular CO-Releasing Molecules on Their CO-Releasing and Anti-Inflammatory Properties
Authors:Yingchun Li  Lars Hemmersbach  Bernhard Krause  Dr. Nikolay Sitnikov  Dr. Anna Schlundt née Göderz  Diego O. Pastene Maldonado  Prof. Dr. Hans-Günther Schmalz  Prof. Dr. Benito Yard
Affiliation:1. Vth medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany

These authors contributed equally to this work.;2. Universität zu Köln, Greinstrasse 4, 50939 Köln, Germany

These authors contributed equally to this work.;3. Universität zu Köln, Greinstrasse 4, 50939 Köln, Germany;4. Vth medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany

Abstract:Over the past decade, a variety of carbon monoxide releasing molecules (CORMs) have been developed and tested. Some CORMs spontaneously release CO once in solution, while others require a trigger mechanism to release the bound CO from its molecular complex. The modulation of biological systems by CORMs depends largely on the spatiotemporal release of CO, which likely differs among the different types of CORMs. In spontaneously releasing CORMs, CO is released extracellularly and crosses the cell membrane to interact with intracellular targets. Other CORMs can directly release CO intracellularly, which may be a more efficient method to modulate biological systems. In the present study, we compared the efficacy of extracellular and intracellular CO-releasing CORMs that either release CO spontaneously or require an enzymatic trigger. The efficacy of such CORMs to modulate HO-1 and VCAM-1 expression in TNF-α-stimulated human umbilical vein endothelial cells (HUVEC) was evaluated.
Keywords:anti-inflammatory agents  heme oxygenases  iron carbonyl complexes  prodrugs  carbon monoxide
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