Cellular evaluation of diselenonicotinamide (DSNA) as a radioprotector against cell death and DNA damage

作者: M. Raghuraman , Prachi Verma , Amit Kunwar , Prasad P. Phadnis , V. K. Jain

DOI: 10.1039/C7MT00034K

关键词:

摘要: Diselenonicotinamide (DSNA), a synthetic organoselenium compound, was evaluated for its radioprotective effect in cellular models. A clonogenic assay Chinese Hamster Ovary (CHO) cells and an apoptosis murine splenic lymphocytes indicated that pre-treatment with DSNA at concentration of 25 μM significantly protected them from radiation-induced cell death. Upon irradiation (1-12 Gy), dose-response studies were carried out under similar treatment conditions, dose modification factor (DMF) estimated to be 1.26. Furthermore, showed effect, even when administered after exposure radiation. Mechanistic investigation revealed increased the intracellular levels GPx GSH irradiated cells. In line this observation, addition pharmacological inhibitor cycle, abrogated activity DSNA. The also complemented by ability prevent DNA damage as monitored micronucleus γ-H2AX assays. did not show much change expressions Nrf2 dependent genes (γ-GCL HO-1), but presence against death damage. Additionally, ATRA inhibited DSNA-mediated up-regulation repair gene RAD51, suggesting possible involvement basal anti-genotoxic conclusion, present study demonstrates radioprotection compound containing nutritionally important moieties like selenium nicotinamide.

参考文章(56)
D. Bartolini, J. Commodi, M. Piroddi, L. Incipini, L. Sancineto, C. Santi, F. Galli, Glutathione S-transferase pi expression regulates the Nrf2-dependent response to hormetic diselenides. Free Radical Biology and Medicine. ,vol. 88, pp. 466- 480 ,(2015) , 10.1016/J.FREERADBIOMED.2015.06.039
H. D. Hurt, E. E. Cary, W. H. Allaway, W. J. Visek, Effect of Dietary Selenium on the Survival of Rats Exposed to Chronic Whole Body Irradiation The Journal of Nutrition. ,vol. 101, pp. 363- 366 ,(1971) , 10.1093/JN/101.3.363
Edith Lubos, Joseph Loscalzo, Diane E. Handy, Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities Antioxidants & Redox Signaling. ,vol. 15, pp. 1957- 1997 ,(2011) , 10.1089/ARS.2010.3586
Atsushi Terada, Minoru Yoshida, Yoshiyuki Seko, Teruaki Kobayashi, Katsumi Yoshida, Masahiro Nakada, Konosuke Nakada, Hirotoshi Echizen, Hiroyasu Ogata, Tadaaki Rikihisa, Active oxygen species generation and cellular damage by additives of parenteral preparations: selenium and sulfhydryl compounds. Nutrition. ,vol. 15, pp. 651- 655 ,(1999) , 10.1016/S0899-9007(99)00119-7
W OSBURN, T KENSLER, Nrf2 signaling: An adaptive response pathway for protection against environmental toxic insults Mutation Research-reviews in Mutation Research. ,vol. 659, pp. 31- 39 ,(2008) , 10.1016/J.MRREV.2007.11.006
Amit Kunwar, S. Jayakumar, H. N. Bhilwade, P. P. Bag, H. Bhatt, R. C. Chaubey, K. I. Priyadarsini, Protective effects of selenocystine against γ-radiation-induced genotoxicity in Swiss albino mice. Radiation and Environmental Biophysics. ,vol. 50, pp. 271- 280 ,(2011) , 10.1007/S00411-011-0352-2