251 - Dihydroxy Selenolane, a Glutathione Peroxidase Mimic as a Radioprotector and an Anti-Inflammatory Agent

Abstract

Radio-protectors are employed to minimize the deleterious effects of ionizing radiations on the normal cells. In recent times, organoselenium compounds are being considered as new class of radio-protectors. Previous studies in our lab showed that dihydroxy selenolane (DHS) exhibits wide range of biological activities such as free radical scavenging, mimicking the function of glutathione peroxidase (GPx) and catalysing the oxidative protein folding reaction.1,2,3 Here DHS was evaluated for its radio-protective activity involving cellular and in vivo model systems. The dosage optimisation indicated that intraperitoneal administration of DHS at 2 mg/Kg body weight starting from five consecutive days prior to irradiation and three times a week during the post irradiation period showed the maximum improvement by 40% in 30 days survival of the mice. DHS administration did not improve haematopoietic parameters, however significantly inhibited radiation induced inflammatory responses in intestine, lung and the circulation. The anti-inflammatory effect of DHS was attributed to increase in the activity of GPx, and the reduction in levels of lipid peroxidation, and pro-inflammatory genes like Icam-1, Ccl-2 and iNos-2. Futher, radioprotection studies in cellular models involving epithelial cells (CHO) and lymphocytes indicated that DHS was effective in preventing the radiation induced cell cycle arrest and subsequent mitotic catastrophe but not the apoptosis. DHS showed signifcant inhibition of radiation induced DNA damage in CHO cells. Taken together, our study proposes that designing selenium compound to induce intra cellular GPx level not only provides radioprotection but also inhibits radiotherapy associated inflammatory side effects. References (1) Kumakura et al., Eur. J. Org. Chem. 3: 440-445, 2010; (2) Singh et al., J. Phys. Chem. A. 114: 8271-8277, 2010; (3) Verma et al.,Toxicol. Res. 5: 434-445, 2016