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

Abstract

Bis(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 radioprotector was attributed to the formation of less reactive intermediates during its oxidation/reduction reactions as evidenced from NMR studies.

Highlights

1. MeImSe, a derivative of selenoneine protects DNA and lipid from radiation damage

2. MeImSe scavenges all major short- and long-lived oxidants involved in radiation toxicity

3. Rate constants of MeImSe for ROS scavenging determined by pulse radiolysis technique

4. First organoselenium compound reported to scavenge nitrogen dioxide radical

5. MeImSe exhibits GPx-like activity through reductive pathway

Keywords:

• Chemical radioprotection
• organoselenium
• kinetic rate constant
• glutathione peroxidase-like activity
• lipid peroxidation

Acknowledgement

The authors acknowledge Dr. Awadhesh Kumar, Head, RPC Division BARC, and Dr. A. K. Tyagi, Director, Chemistry Group, BARC for their support and encouragement.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.