title: Differential Effects of CORM-2 and CORM-401 in Murine Intestinal Epithelial MODE-K Cells under Oxidative Stress.
abstract: Carbon monoxide (CO)-releasing molecules (CO-RMs) are intensively studied to provide cytoprotective and anti-inflammatory effects of CO in inflammatory conditions including intestinal inflammation. The water-soluble CORM-A1 reduced apoptosis and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) induced by tumor necrosis factor (TNF)-α/cycloheximide (CHX) in mouse MODE-K intestinal epithelial cells (IECs), without influencing TNF-α/CHX-induced mitochondrial superoxide anion ([Formula: see text]). The aim of the present study in the same model was to comparatively investigate the influence of lipid-soluble CORM-2 and water-soluble CORM-401, shownin vitroto release more CO under oxidative conditions. CORM-2 abolished TNF-α/CHX-induced total cellular ROS whereas CORM-401 partially reduced it, both partially reducing TNF-α/CHX-induced cell death. Only CORM-2 increased mitochondrial [Formula: see text] production after 2 h of incubation. CORM-2 reduced TNF-α/CHX-, rotenone- and antimycin-A-induced mitochondrial [Formula: see text] production; CORM-401 only reduced the effect of antimycin-A. Co-treatment with CORM-401 during 1 h exposure to H2O2reduced H2O2(7.5 mM)-induced ROS production and cell death, whereas CORM-2 did not. The study illustrates the importance of the chemical characteristics of different CO-RMs. The lipid solubility of CORM-2 might contribute to its interference with TNF-α/CHX-induced mitochondrial ROS signaling, at least in mouse IECs. CORM-401 is more effective than other CO-RMs under H2O2-induced oxidative stress conditions.
authors.affiliation: Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University Ghent, Belgium.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Babu
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University Ghent, Belgium.
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.affiliation: INSERM U955, Faculty of Medicine, Equipe 12 and University Paris Est Créteil, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
authors.affiliation: Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University Ghent, Belgium.
authors.forename: Romain A
authors.initials: RA
authors.lastname: Lefebvre
keywords: TNF-α/CHX; carbon monoxide-releasing molecules; hydrogen peroxide; intestinal epithelial cells; mitochondria; oxidative stress; reactive oxygen species; solubility