Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy

  • Salehi, Samie (Department of Chemistry, Ferdowsi University of Mashhad, Faculty of Science) ;
  • Saljooghi, Amir Sh. (Department of Chemistry, Ferdowsi University of Mashhad, Faculty of Science) ;
  • Badiee, Somayeh (Department of Chemistry, Ferdowsi University of Mashhad, Faculty of Science) ;
  • Moqadam, Mojtaba Mashmool (Department of Chemistry, Ferdowsi University of Mashhad, Faculty of Science) ;
  • Received : 2017.02.20
  • Accepted : 2017.07.07
  • Published : 2017.10.15
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Abstract

Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats' organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

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References

  1. Ryu, H.W., Lee, D.H., Won, H., Kim, K.H., Seong, Y.J. and Kwon, S.H. (2015) Influence of toxicologically relevant metals on human epigenetic regulation. Toxicol. Res., 31, 1-9. https://doi.org/10.5487/TR.2015.31.1.001
  2. Lan, C.H. and Lin, T.S. (2005) Acute toxicity of trivalent thallium compounds to Daphnia magna. Ecotoxicol. Environ. Saf., 61, 432-435. https://doi.org/10.1016/j.ecoenv.2004.12.021
  3. Hoffman, R.S. (2003) Thallium toxicity and the role of Prussian blue in therapy. Toxicol. Rev., 22, 29-40. https://doi.org/10.2165/00139709-200322010-00004
  4. Rodriguez-Mercado, J.J. and Altamirano-Lozano, M.A. (2013) Genetic toxicology of thallium: a review. Drug Chem. Toxicol., 36, 369-383. https://doi.org/10.3109/01480545.2012.710633
  5. Xiao, T., Guha, J., Boyle, D., Liu, C.Q. and Chen, J. (2004) Environmental concerns related to high thallium levels in soils and thallium uptake by plants in southwest Guizhou, China. Sci. Total Environ., 318, 223-244. https://doi.org/10.1016/S0048-9697(03)00448-0
  6. Peter, A.L. and Viraraghavan, T. (2005) Thallium: a review of public health and environmental concerns. Environ. Int., 3, 493-501.
  7. Atlas, E., Fishbein, L., Giam, C.S., Leonard, J.E., Muir, D.C.G., Powers, M.A., Jr. and Schoer, J. (1984) Handbook of environmental chemistry; volume 3 part C. (Hutzinger, O. Ed.). Springer-Verlag, New York, pp. 143-214.
  8. Abdel-Daim, M.M. and Abdou, R.H. (2015) Protective effects of diallyl sulfide and curcumin separately against thalliuminduced toxicity in rats. Cell J., 17, 379-388.
  9. Riyaz, R., Pandalai, S.L., Schwartz, M. and Kazzi, Z.N. (2013) A fatal case of thallium toxicity: challenges in management. J. Med. Toxicol., 9, 75-78. https://doi.org/10.1007/s13181-012-0251-1
  10. Clarke, E.T. and Martell, A. E. (1992) Stabilities of 1,2-dimethyl-3-hydroxy-4-pyridinone chelates of divalent and trivalent metal ions. Inorg. Chim. Acta, 191, 57-63. https://doi.org/10.1016/S0020-1693(00)80327-8
  11. Gomez, W., Esparza, J.L., Domingo, J.L., Corbella, J., Singh, P.K. and Jones, M.M. (1998) Aluminium distribution and excretion: a comparative study of a number of chelating agents in rats. Pharmacol. Toxicol., 82, 295-300. https://doi.org/10.1111/j.1600-0773.1998.tb01576.x
  12. Heinz, U., Hegetschweiler, K., Acklin, P., Faller, B., Lattmann, R. and Schnebli, H.P. (1999) 4-[3,5-Bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl]- benzoic acid: a novel, efficient and selective iron (III) complexing agent. Angew. Chem. Int. Ed., 38, 2568-2570. https://doi.org/10.1002/(SICI)1521-3773(19990903)38:17<2568::AID-ANIE2568>3.0.CO;2-C
  13. Steinhauser, S., Heinz, U., Bartholomä, M., Weyhermüller, T., Nick, H. and Hegetschweiler, K. (2004) Complex formation of ICL670 and related ligands with FeIII and FeII. Eur. J. Inorg. Chem., 2004, 4177-4192.
  14. Yang, L.P.H., Keam, S.J. and Keating, G.M. (2007) Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs, 67, 2211-2230. https://doi.org/10.2165/00003495-200767150-00007
  15. Kontoghiorghes, G.J. (1995) New concepts of iron and aluminium chelation therapy with oral L1 (deferiprone) and other chelators. A review. Analyst, 120, 845-851. https://doi.org/10.1039/an9952000845
  16. Liu, Z.D. and Hider, R.C. (2002) Design of iron chelators with therapeutic application. Coord. Chem. Rev., 232, 151-171. https://doi.org/10.1016/S0010-8545(02)00050-4
  17. Tenenbein, M. (2005) Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch. Pediatr. Adolesc. Med., 159, 557-560. https://doi.org/10.1001/archpedi.159.6.557
  18. Eom, S.Y., Lim, J.A., Kim, Y.D., Choi, B.S., Hwang, M.S., Park, J.D., Kim, H. and Kwon, H.J. (2016) Allele frequencies of the single nucleotide polymorphisms related to the body burden of heavy metals in the korean population and their ethnic differences. Toxicol. Res., 32, 195-205. https://doi.org/10.5487/TR.2016.32.3.195
  19. Galanello, R., Agus, A., Campus, S., Danjou, F., Giardina, P.J. and Grady, R.W. (2010) Combined iron chelation therapy. Ann. N. Y. Acad. Sci., 1202, 79-86. https://doi.org/10.1111/j.1749-6632.2010.05591.x
  20. Salehi, S., Saljooghi, A.S. and Shiri, A. (2016) Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator. Eur. J. Pharmacol., 781, 209-217. https://doi.org/10.1016/j.ejphar.2016.04.026
  21. Voskaridou, E., Christoulas, D. and Terpos, E. (2011) Successful chelation therapy with the combination of deferasirox and deferiprone in a patient with thalassaemia major and persisting severe iron overload after single-agent chelation therapies. Br. J. Haematol., 154, 654-656. https://doi.org/10.1111/j.1365-2141.2011.08626.x
  22. Harriss, W.R. and Messori, L. (2002) A comparative study of aluminum(III), gallium(III), indium(III), and thallium(III) binding to human serum transferrin. Coord. Chem. Rev., 228, 237-262. https://doi.org/10.1016/S0010-8545(02)00037-1
  23. Saljooghi, A.S. and Fatemi, S.J. (2010) Clinical evaluation of Deferasirox for removal of cadmium ions in rat. Biometals, 23, 707-712. https://doi.org/10.1007/s10534-010-9337-x
  24. Balooch, F.D., Fatemi, S.J. and Iranmanesh, M. (2014) Combined chelation of lead (II) by deferasirox and deferiprone in rats as biological model. BioMetals, 27, 89-95. https://doi.org/10.1007/s10534-013-9689-0
  25. Saljooghi, A.S. and Fatemi, S.J. (2010) Removal of thallium by deferasirox in rats as biological model. J. Appl. Toxicol., 31, 139-143.
  26. Fatemi, S.J., Saljooghi, A.S., Balooch, F.D., Iranmanesh, M. and Golbafan, M.R. (2011) Chelation of cadmium by combining deferasirox and deferiprone in rats. Toxicol. Ind. Health, 27, 371-377. https://doi.org/10.1177/0748233710388451
  27. Amiri, A., Fatemi, S.J. and Fatemi, S.N. (2007) Removal of thallium by combining desferrioxamine and deferiprone chelators in rats. Biometals, 20, 159-163. https://doi.org/10.1007/s10534-006-9023-1
  28. Tubafard, S. and Fatemi, S.J. (2008) Chelation of bismuth by combining desferrioxamine and deferiprone in rats. Toxicol. Ind. Health, 24, 235-240. https://doi.org/10.1177/0748233708095771
  29. Iranmanesh, M., Fatemi, S.J., Ebrahimpour, R. and Balooch, F.D. (2013) Chelation of chromium(VI) by combining Deferasirox and deferiprone in rats. Biometals, 26, 465-471. https://doi.org/10.1007/s10534-013-9631-5