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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- DFX:
-
Deferasirox
- L1:
-
Deferiprone
- DFO:
-
Desferrioxamine
- BCT:
-
Before chelation therapy
- WCT:
-
Without chelation therapy
- CT:
-
Chelation therapy
- TIBC:
-
Total iron binding capacity
- TS:
-
Transferrin saturation
References
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.
Lan, C.H. and Lin, T.S. (2005) Acute toxicity of trivalent thallium compounds to Daphnia magna. Ecotoxicol. Environ. Saf., 61, 432–435.
Hoffman, R.S. (2003) Thallium toxicity and the role of Prussian blue in therapy. Toxicol. Rev., 22, 29–40.
Rodriguez-Mercado, J.J. and Altamirano-Lozano, M.A. (2013) Genetic toxicology of thallium: a review. Drug Chem. Toxicol., 36, 369–383.
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.
Peter, A.L. and Viraraghavan, T. (2005) Thallium: a review of public health and environmental concerns. Environ. Int., 3, 493–501.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Liu, Z.D. and Hider, R.C. (2002) Design of iron chelators with therapeutic application. Coord. Chem. Rev., 232, 151–171.
Tenenbein, M. (2005) Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch. Pediatr. Adolesc. Med., 159, 557–560.
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.
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.
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.
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.
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.
Saljooghi, A.S. and Fatemi, S.J. (2010) Clinical evaluation of Deferasirox for removal of cadmium ions in rat. Biometals, 23, 707–712.
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.
Saljooghi, A.S. and Fatemi, S.J. (2010) Removal of thallium by deferasirox in rats as biological model. J. Appl. Toxicol., 31, 139–143.
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.
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.
Tubafard, S. and Fatemi, S.J. (2008) Chelation of bismuth by combining desferrioxamine and deferiprone in rats. Toxicol. Ind. Health, 24, 235–240.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Salehi, S., Saljooghi, A.S., Badiee, S. et al. Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy. Toxicol Res. 33, 299–304 (2017). https://doi.org/10.5487/TR.2017.33.4.299
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.5487/TR.2017.33.4.299