Abstract
Background and Objectives
3,3′ Diseleno dipropionic acid (DSePA), a synthetic compound has been shown to have radioprotective activity, especially as a lung radioprotector. In this study, the pharmacokinetics and biodistribution of DSePA in MX-1 tumour bearing SCID mice were evaluated.
Methods
Twenty SCID mice were administered DSePA (50 mg/kg bodyweight) by oral gavage following which four animals each were sacrificed at 15, 30 min, 1, 2 and 4 h. Blood and tissue samples were collected for determination of DSePA concentration by graphite furnace atomic absorption spectrometry (GFAAS) method. The control group (n = 4) was administered sterile water and sacrificed at 4 h.
Results
Peak plasma concentration (C max) of 2.7 µg/ml was observed at 15 min which returned to near baseline (baseline = 0.6 µg/ml) at 1 h following drug administration. Biphasic pharmacokinetics characterized by rapid distribution phase and a slower elimination phase were observed. Highest maximal concentration (C max) of the drug was observed in lung (19.2 µg/g at 30 min) followed by intestine (14.64 µg/g at 15 min) and kidney (12.96 µg/g at 15 min). There was negligible uptake in tumor tissue and no uptake in brain.
Conclusions
DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.
References
Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007;12(6):738–47.
Kunwar A, Mishra B, Barik A, Kumbhare LB, Pandey R, Jain VK, Priyadarshini KI. 3,3′-Diselenodipropionic acid, an efficient peroxyl radical scavenger and a GPx mimic, protects erythrocytes (RBCs) from AAPH-induced hemolysis. Chem Res Toxicol. 2007;20(10):1482–7.
Kunwar A, Bansal P, Kumar SJ, Bag PP, Paul P, Reddy ND, Kumbhare LB, Jain VK, Chaubey RC, Unnikrishnan MK, Priyadarshini KI. In vivo radioprotection studies of 3,3′-diselenodipropionic acid, a selenocystine derivative. Free Radic Biol Med. 2010;48(3):399–410.
Chaurasia RK, Balakrishnan S, Kunwar A, Yadav U, Bhat N, Anjaria K, Nairy R, Sapra BK, Jain VK, Priyadarshini KI. Cyto-genotoxicity assessment of potential radioprotector, 3,3′-diselenodipropionic acid (DSePA) in Chinese Hamster Ovary (CHO) cells and human peripheral blood lymphocytes. Mutat Res Gen Toxicol Environ Mutagen. 2014;774:8–16.
Kunwar A, Jain VK, Priyadarsini KI, Haston CK. A selenocysteine derivative therapy affects radiation-induced pneumonitis in the mouse. Am J Resp Cell Mol Bol. 2013;49(4):654–61.
Suzuki KT, Somekawa L, Kurasaki K, Suzuki N. Simultaneous tracing of 76Se-selenite and 77Se-selenomethionine by absolute labeling and speciation. Toxicol Appl Pharm. 2006;217:43–50.
Zhou HY, Dou GF, Meng ZY, Lou YQ, Zhang GL. High performance liquid chromatographic determination of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]-ethane (BBSKE), a novel organoselenium compound, in dog plasma using pre-column derivatization and its application in pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;852:617–24.
Muller A, Gabriel H, Sies H, Terlinden R, Fischer H, Romer A. A novel biologically active selenooorganic compound–VII. Biotransformation of ebselen in perfused rat liver. Biochem Pharmacol. 1988;37:1103–09.
Li YH, Zhang GZ, Huang RH, Li DD, Luo YU, Yang Y, et al. Study on tissue distribution of a novel organoselenium antitumor compound WBSELEN. J Chin Pharm Sci. 2011;20:578–83.
Kunwar A, Bag PP, Chattopadhyay S, Jain VK, Priyadarsini KI. Anti-apoptotic, anti-inflammatory, and immunomodulatory activities of 3,3′-diselenodipropionic acid in mice exposed to whole body gamma-radiation. Arch Toxicol. 2011;85(11):1395–405.
Wendel A, Fausel M, Safayhi H, Tiegs G, Otter R. A novel biologically active seleno-organic compound—II: activity of PZ 51 in relation to Glutathione Peroxidase. Biochem Pharmacol. 1984;33(20):3241–5.
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No sources of funding were used to conduct this study.
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The study was approved by the Institutional Animal Ethics Committee of ACTREC.
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Gota, V., Goda, J.S., Doshi, K. et al. Biodistribution and Pharmacokinetic Study of 3,3′ Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice. Eur J Drug Metab Pharmacokinet 41, 839–844 (2016). https://doi.org/10.1007/s13318-015-0301-6
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DOI: https://doi.org/10.1007/s13318-015-0301-6