Bis(1-methylimidazol-2-yl) diselenide and its evaluation as a chemical radio-protector: role of kinetic rate constants for ROS scavenging and glutathione peroxidase like activity

Free Radic Res. 2024 Jan 2:1-14. doi: 10.1080/10715762.2023.2299341. Online ahead of print.ABSTRACTBis(1-methylimidazol-2-yl) diselenide (MeImSe), a derivative of selenoneine, has been examined for bimolecular rate constants for scavenging of various radiolytically and non-radiolytically generated reactive oxygen species (ROS). Further, its potential to show glutathione peroxidase (GPx)-like activity and to protect in vitro models of DNA and lipid against radiation induced strand breakage and lipid peroxidation, respectively were studied. The results confirmed that MeImSe scavenged all major short-lived (hydroxyl radical) and long-lived (peroxyl radical, carbonate radical, nitrogen dioxide radical, hypochlorite and hydrogen peroxide) oxidants involved in the radiation toxicity either directly or through GPx-like catalytic mechanism. The rate constants of MeImSe for these oxidants were found to be comparable to analogous sulfur and selenium-based compounds. The enzyme kinetics study established that MeImSe took part in the GPx cycle through the reductive pathway. Further, MeImSe inhibited the radiation induced DNA strand cleavage and lipid peroxidation with half maximal inhibitory concentration (IC50) of ∼ 60 μM and ∼100 μM, respectively. Interestingly, MeImSe treatment in the above concentration range (>100 μM) did not show any significant toxicity in normal human lung fibroblast (WI26) cells. The balance between efficacy and toxicity of MeImSe as a chemical radiopr...
Source: Free Radical Research - Category: Research Authors: Source Type: research