Differential Effects of CORM-2 and CORM-401 in Murine Intestinal Epithelial MODE-K Cells under Oxidative Stress

• Published in: Frontiers in pharmacology Vol. 8; p. 31
• Main Authors: Babu, Dinesh, Leclercq, Georges, Motterlini, Roberto, Lefebvre, Romain A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08-02-2017
• Subjects: Pharmacology; intestinal epithelial cells; carbon monoxide-releasing molecules; mitochondria; hydrogen peroxide; reactive oxygen species; solubility; TNF-α/CHX; oxidative stress
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2017.00031

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, shown
to 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 H
O
reduced H
O
(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 H
O
-induced oxidative stress conditions.