Evaluation of the anti-oxidant properties of a SOD-mimic Mn-complex in activated macrophages

Abstract

SOD-mimics are small complexes that reproduce the activity of superoxide dismutases, natural proteins that catalytically dismutate the superoxide anion. Activated macrophages, which produce ROS and RNS fluxes, constitute a relevant model to challenge antioxidant activity in a cellular context and were used to test a Mn-complex which was shown to efficiently alter the flow of O(2)(-), ONOO(-) and H(2)O(2).

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

“…Since most SOD mimics display a variety of activities and do not selectively react with O 2 -, reported beneficial effects can be attributed to actions other than superoxide scavenging (54). Similar shortcomings apply to cell culture systems in which O 2 -, along with other reactive oxygen species (ROS), are generated by the addition of chemical agents (84,101), enzymatically (xanthine plus xanthine oxidase) (84), by radiation exposure (110); by activation of macrophages (33), and so on. The lack of a clear understanding of both the nature of the ROS responsible for damage and the mechanisms of action of the tested compounds can be listed among the reasons for failures in clinical trials (8,23,38,44,52,76,109).…”

A new mononuclear manganese(III) complex of an unsymmetrical hexadentate N3O3 ligand exhibiting superoxide dismutase and catalase-like activity: synthesis, characterization, properties and kinetics studies

“…The intrinsic dinuclear nature of the MnCAT active site has stimulated activity studies on complexes of binucleating ligands which provide an internal bridge to stabilize the dimanganese unit [6,16]. However, a number of mononuclear Mn complexes have shown CAT activity, for which efficiency seems to be related to the presence of at least one labile coordination position on the Mn ion [7][8][9][10][11][12][13][14][15][17][18][19]. This kind of mononuclear catalytic antioxidants has been proposed to react through a mechanism involving mononuclear Mn V = O species [20,21] or through formation of dimeric species in solution [22].…”

“…Among them, several complexes have been reported to have dual SOD/CAT activity [7][8][9][10][11][12][13][14][15], an advantageous property since cytotoxic H 2 O 2 is produced during O 2…”

Biological applications of the electrochemical sensing of nitric oxide: fundamentals and recent developments

“…With this technique, accuracy in the positioning of the sensor can be achieved down to 5 μ m from the surface of a single HUVEC. The dependence of the current measured upon bradykinin stimulation, indicating the flux of NO released from the Amatore et al, 2000Amatore et al, , 2001Amatore et al, , 2006bAmatore et al, , 2008aAmatore et al, ,b,c, 2010aArbault et al, 2004;Verchier et al, 2007;Ferreira et al, 2009;Tapsoba et al, 2009;Filipov í c et al, 2010 ;Hu et al , 2010 ;Bernard et al , 2012 cell, over the distance to the cell can be characterized ( Figure 1A). It was later shown that the use of the shearforce-based constant distance mode of the SECM allowed the topology of the cell to be resolved and enabled the positioning of the sensor at its apex.…”

“…These compounds were also found to scavenge peroxynitrite and sometimes NO to nitrite, thus removing these very reactive, toxic species and converting them into less active compounds (Filipov í c et al, 2010 ;Bernard et al , 2012 ).…”