Back to Search
Start Over
Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2021 Jun; Vol. 219, pp. 111431. Date of Electronic Publication: 2021 Mar 19. - Publication Year :
- 2021
-
Abstract
- Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2'-n-butoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP <superscript>5+</superscript> ) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5,6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1,4, 7,10] tetraazacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N'-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP <superscript>5+</superscript> , M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antioxidants metabolism
Cell Line
Glutathione Peroxidase metabolism
Humans
Hydrogen Peroxide metabolism
Metalloporphyrins metabolism
Molecular Mimicry
Oxidation-Reduction
Oxidative Stress
Porphyrins metabolism
Reactive Oxygen Species metabolism
Superoxides metabolism
Catalase metabolism
Manganese metabolism
Organometallic Compounds metabolism
Superoxide Dismutase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 219
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33798828
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2021.111431