BioMetals

, Volume 26, Issue 3, pp 465–471

Chelation of chromium(VI) by combining deferasirox and deferiprone in rats

  • Marzieh Iranmanesh
  • S. Jamil A. Fatemi
  • Roza Ebrahimpour
  • Faezeh Dahooee Balooch
Article

Abstract

The present research is aimed to characterize the potential efficiency of two chelators after chromium(VI) administration for 60 days following two doses of 15 and 30 mg/kg chromium(VI) per body weight daily to male rats. However, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing chromium(VI) from rat organs was considered. In this way, two known chelators deferasirox and deferiprone were chosen and given orally as a single or combined therapy for a period of 1 week. Chromium(VI) and iron concentrations in tissues were determined by flame atomic absorption spectroscopy. The combined chelation therapy results show that deferasirox and deferiprone are able to remove chromium(VI) ions from various tissues while iron concentration returned to normal levels and symptoms also decreased.

Keywords

Deferasirox Deferiprone Chromium toxicity Chelation therapy Rats 

References

  1. Agency for Toxic Substances and Diseases Registry (ATSDR) (1998) Toxicological profile for chromium. Public Health Service. US Department of Health and Human Services, AtlantaGoogle Scholar
  2. Amiri A, Fatemi SJ, Fatemi SN (2007) Removal of thallium by combining desferrioxamine and deferiprone chelators in rats. Biometals 20:159–163CrossRefPubMedGoogle Scholar
  3. Bagchi D, Stohs SJ, Downs BW, Bagchi M, Preuss HG (2002) Cytotoxicity and oxidative mechanisms of different forms of chromium. Toxicology 180:5–22CrossRefPubMedGoogle Scholar
  4. Cappellini MD (2008) Long-term efficacy and safety of deferasirox. Blood Rev 2:35–41CrossRefGoogle Scholar
  5. Clarke ET, Martell AE (1992) Stabilities of 1, 2-dimethyl-3-hydroxypyrid-4-one chelates of divalent and trivalent metal ions. Inorg Chim Acta 19:57–63CrossRefGoogle Scholar
  6. Codd R, Dillon CT, Levina A, Lay PA (2001) Studies on the genotoxicity of chromium: from the test tube to the cell. Coord Chem Rev 216–217:537–582CrossRefGoogle Scholar
  7. Evans RW, Kong X, Hider RC (2012) Iron mobilization from transferrin by therapeutic iron chelating agents. Biochim Biophys Acta 1820:282–290CrossRefPubMedGoogle Scholar
  8. Fatemi SJ, Amiri A, Bazargan MH, Tubafard S, Fatemi SN (2007) Clinical evaluation of desferrioxamine (DFO) for removal of thallium ions in rats. Int J Artif Organs 30:902–905PubMedGoogle Scholar
  9. Fatemi SJ, Tubafard S, Nadi B (2009) Evaluation of the effect of cadmium on rat organs and investigation of diethyl carbamate as an oral drug in treatment of cadmium toxicity. Med Chem Res 18:179–186CrossRefGoogle Scholar
  10. Flora SJS, Bhattacharyan R, Vijayaraghavan R (1995) Combined therapeutic potential of meso dimercaptosuccinic acid and calcium edentate on the mobilization and distribution of lead in experimental lead intoxication in rats. Fundam Appl Toxicol 25:233–240CrossRefPubMedGoogle Scholar
  11. Galanello R, Agus A, Campus S, Danjou F, Giardina PJ, Grady RW (2010) Combined iron chelation therapy. Ann N Y Acad Sci 1202:79–86CrossRefPubMedGoogle Scholar
  12. Glickstein H, BenEl R, Link G, Breuer W, Konijn AM, Hershko C, Nick H, Cabantchik ZI (2006) Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood 108:3195–3203CrossRefPubMedGoogle Scholar
  13. Gomez W, Esparza JL, Domingo JL, Singha PK, Jones MM (1988) Comparative aluminium mobilizing action of desferrioxamine and four 3-hydroxypyrid-4-ones in aluminium-loaded rats. Toxicology 130:175–181CrossRefGoogle Scholar
  14. Gyparaki M, Porter JB, Hirani S, Streater M, Hider RC, Huehns ER (1987) In vivo evaluation of hydroxypyridone iron chelators in a mouse model. Acta Haematol 78:217–221CrossRefPubMedGoogle Scholar
  15. Heinz U, Hegetschweiler K, Acklin P, Faller B, Lattmann R, Schnebli HP (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 Edit 38:2568–2571CrossRefGoogle Scholar
  16. Hershko C, Konijn AM, Nick HP, Breuer W, Cabantchik ZI, Link G (2001) ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture. Blood 97:1115–1122CrossRefPubMedGoogle Scholar
  17. Hider RC, Kontoghiorghes G, Silver J (1984) Pharmaceutical compositions. GB patent 2118176 AGoogle Scholar
  18. Kaur G, Srivastava UC, Dwivedi RS, Srivastava RC (1984) Influence of polyaminocarboxylic acids on the removal of manganese-54 from the body organs of sham-operated and partially hepatectomized rats. Toxicol Lett 22:1–6CrossRefPubMedGoogle Scholar
  19. Kimbrough DE, Cohen Y, Winer AM (1999) A critical assessment of chromium in the environment. Crit Rev Environ Sci Technol 29:1–46CrossRefGoogle Scholar
  20. Kontoghiorghes GJ, Aldouri MA, Hoffbrand AV, Barr J, Wonke B, Kourouclaris T, Sheppard L (1987) Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Br Med J 295:1509–1512CrossRefGoogle Scholar
  21. Ma Y, Zhou T, Kong X, Hider RC (2012) Chelating agents for the treatment of systemic iron overload. Curr Med Chem 19:2816–2827CrossRefPubMedGoogle Scholar
  22. Neufeld EJ (2006) Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 107(9):3436–3441CrossRefPubMedGoogle Scholar
  23. Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ, Sechaud R (2003) Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a placebo-controlled, dose-escalation trial. Lancet 361:1597–1602CrossRefPubMedGoogle Scholar
  24. O’Brien TJ, Ceryak S, Patierno SR (2003) Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res 533:3–36CrossRefPubMedGoogle Scholar
  25. Shokooh Saljooghi A, Fatemi SJ (2010) Clinical evaluation of deferasirox for removal of cadmium ions in rat. Biometals 23:707–712CrossRefGoogle Scholar
  26. Steinhauser S, Heinz U, Bartholoma M, Weyhermu¨ller T, Nick H, Hegetschweiler K (2004) Complex formation of ICL670 and related ligands with Fe(III) and Fe(II). Eur J Inorg Chem 21:4177–4192CrossRefGoogle Scholar
  27. Tubafard S, Fatemi SJ (2008) Chelation of bismuth by combining desferrioxamine and deferiprone in rats. Toxicol Ind Health 24:235–240CrossRefPubMedGoogle Scholar
  28. Voskaridou E, Christoulas D, 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 154:654–656CrossRefPubMedGoogle Scholar
  29. Yang LPH, Keam SJ, Keating GM (2007) Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs 67:2211–2230CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Marzieh Iranmanesh
    • 1
  • S. Jamil A. Fatemi
    • 1
  • Roza Ebrahimpour
    • 1
  • Faezeh Dahooee Balooch
    • 1
  1. 1.Chemistry DepartmentShahid Bahonar University of KermanKermanIran

Personalised recommendations