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Combined chelation of lead (II) by deferasirox and deferiprone in rats as biological model

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Abstract

In order to investigate the capability of two chelators deferasirox (DFX or ICL670) and deferiprone (L1) in removing lead from the body, the present research was performed. Two does levels of 40 and 80 mg/kg body weight of lead (II) chloride was given to rats as biological model for 45 days. After 45 days, some toxicity symptoms were observed in rats such as loss of hair and weight, appearance of red dots around eyes, weakness and irritability. After lead application, chelation therapy with DFX and L1 as mono and combined (DFX, L1 and DFX + L1) was done for 10 days. After chelation therapy, lead level in different tissues reduced. The combined chelation therapy results showed that these chelators are able to remove lead from the body and toxicity symptoms decreased. The combined therapy results (DFX + L1) show higher efficacy and lower toxicity compared to single therapies.

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References

  • Aboul-Enein AM, AbouElella FN, Abdullah ES (2010) Monitoring of some organochlorines and organophosphorus residues in imported and locally raised chicken and bovine muscles in Egypt. J Appl Sci Res 6(6):600–608

    CAS  Google Scholar 

  • Afify AMR, El-Beltagi HS (2011) Effect of the insecticide cyanophos on liver function in adult male rats. Fresen Environ Bull 20(4a):1084–1088

    CAS  Google Scholar 

  • Amiri A, Fatemi SJ, Fatemi SN (2007) Removal of thallium by combining desferrioxamine and deferiprone chelators in rats. Biometals 20(2):159–163

    Article  CAS  PubMed  Google Scholar 

  • Cappellini MD (2008) Long-term efficacy and safety of deferasirox. Blood Rev 22:35–41

    Article  Google Scholar 

  • Devanur LD, Neubert H, Hider RC (2008) The fenton activity of iron(III) in the presence of deferiprone. J Pharm Sci 97:1454–1467

    Article  CAS  PubMed  Google Scholar 

  • Ding Y, Gonick HC, Vaziri ND, Liang K, Wei L (2001) Lead-induced hypertension. III. Increased hydroxyl radical production. Am J Hypertens 14(2):169–173

    Article  CAS  PubMed  Google Scholar 

  • El-Beltagi HS, Mohamed AA, Rashed MM (2010) Response of antioxidative enzymes to cadmium stress in leaves and roots of radish (Raphanus sativus L.). Not Sci Biol 2(4):76–82

    CAS  Google Scholar 

  • Evans RW, Kong X, Hider RC (2012) Iron mobilization from transferrin by therapeutic iron chelating agents. Biochim Biophys Acta 1820:282–290

    Article  CAS  PubMed  Google Scholar 

  • Fatemi SJ, Amiri A, Bazargan MH, Tubafard S, Fatemi SN (2007) Clinical evaluation of desferrioxamine (DFO) for removal of thallium ions in rat. Int J Artif Org 30:902–905

    CAS  Google Scholar 

  • 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(3):179–186

    Article  Google Scholar 

  • Fatemi SJ, Sh Saljooghi A, Dahooee BF, Iranmanesh M, Golbafn MR (2011) Chelation of cadmium by combining deferasirox and deferiprone in rats. Toxicol Ind Health 27(4):371–377

    Article  CAS  Google Scholar 

  • Fatemi SJ, Saljooghi AS, Balooch FD, Iranmanesh M, Golbafan MR (2012) Removal of cadmium by combining deferasirox and desferrioxamine chelators in rats. Toxicol Ind Health 28(1):35–41

    Article  CAS  PubMed  Google Scholar 

  • Galanello R, Agus A, Campus S, Danjou F, Giardina PJ, Grady RW (2010) Combined iron chelation therapy. Ann NY Acad Sci 1202:79–86

    Article  CAS  PubMed  Google Scholar 

  • 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 108:3195–3203

    Article  CAS  PubMed  Google Scholar 

  • 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(4):1115–1122

    Article  CAS  PubMed  Google Scholar 

  • Hider RC, Kontoghiorghes G, Silver J (1984) Pharmaceutical compositions. UK patent 2,118,176A

  • Hinc Y ilmaz MD, Alper Keten MD, Emre Karacaoglu MD, Engin Tutkun MD, Ramazan Akçan MD (2012) Analysis of the hematological and biochemical parameters related to lead intoxication. J Forensic Legal Med 19(8):452–454

    Article  Google Scholar 

  • Hoffbrand AV, Cohn A, Hershko C (2003) Role of deferiprone in chelation therapy for transfusional iron overload. Blood 102:17–24

    Article  CAS  PubMed  Google Scholar 

  • Hsu PC, Guo YL (2002) Antioxidant nutrients and lead toxicity. Toxicology 180(1):33–44

    Article  CAS  PubMed  Google Scholar 

  • Ibrahim NM, Eweis EA, El-Beltagi HS, Abdel-Mobdy YE (2012) Effect of lead acetate toxicity on experimental male albino rat. Asian Pac J Trop Biomed 2(1):41–46. doi:10.1016/S2221-1691(11)60187-1

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Iranmanesh M, Fatemi SJ, Ebrahimpour R, Dahooee FB (2013) Chelation of chromium (VI) by combining deferasirox and deferiprone in rats. Biometals 26(3):465–471

    Article  CAS  PubMed  Google Scholar 

  • Kennish MJ (1992) Ecology of estuaries: anthropogenic effects. CRC Press, Boca Raton. ISBN 9780849380419

    Google Scholar 

  • Kontoghiorghes GJ, Sheppard L (1987) Simple synthesis of the potent chelators 1-alkyl-3- hydroxy-2-mehylpyrid-4-ones. Inorg Chim Acta 136:111–112

    Article  Google Scholar 

  • Kontoghiorghes GJ, Aldouri MA, Hoffbrand AV (1987) Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Br Med J 295:1509–1512

    Article  CAS  Google Scholar 

  • Ma Y, Zhou T, Kong X, Hider RC (2012) Chelating agents for the treatment of systemic iron overload. Curr Med Chem 19:2816–2827. doi:10.2174/092986712800609724

    Article  CAS  PubMed  Google Scholar 

  • Malecka A, Jarmuszkiewicz W, Tomaszewska B (2001) Antioxidative defense to lead stress in sub cellular compartments of pea root cells. Acta Biochim Pol 48:687–698

    CAS  PubMed  Google Scholar 

  • Mohamed AA, El-Beltagi HS, Rashed MM (2009) Cadmium stress induced change in some hydrolytic enzymes, free radical formation and ultrastructural disorders in radish plant. Electron J Environ Agric Food Chem 8(10):967–983

    Google Scholar 

  • Navarro-Moreno LG, Quintanar-Escorza MA, Gonzalez S, Mondragon R, Cerbon-Solorzano J, Valdes J, Calderon-Salinas JV (2009) Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells. Toxicol In Vitro 23(7):1298–1304

    Article  CAS  PubMed  Google Scholar 

  • Neufeld EJ (2006) Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 107(9):3436–3441

    Article  CAS  PubMed  Google Scholar 

  • Pande M, Mehta A, Pant BP, Flora SJ (2001) Combined administration of a chelating agent and an antioxidant in the prevention and treatment of acute lead intoxication in rats. Environ Toxicol Pharm 9(4):173–184

    Article  CAS  Google Scholar 

  • Saljooghi AS, Fatemi SJ (2010) Clinical evaluation of Deferasirox for removal of cadmium ions in rat. Biometals 23(4):707–712

    Article  CAS  PubMed  Google Scholar 

  • Saljooghi AS, Fatemi SJ (2011) Removal of thallium by deferasirox in rats as biological model. J Appl Toxicol 31(2):139–143

    CAS  PubMed  Google Scholar 

  • Sansar W, Ahboucha S, Gamrani H (2011) Chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat. Acta Histochem 113(6):601–607. doi:10.1016/j.acthis.2010.06.005

    Article  CAS  PubMed  Google Scholar 

  • Tubafard S, Fatemi SJ (2008) Chelation of bismuth by combining desferrioxamine and deferiprone in rats. Toxicol Ind Health 24(4):235–240

    Article  CAS  PubMed  Google Scholar 

  • Tubafard S, Fatemi SJ, Saljooghi AS, Torkzadeh M (2010) Removal of vanadium by combining desferrioxamine and deferiprone chelators in rats. Med Chem Res 19:854–863. doi:10.1007/s00044-009-9235-3

    Article  CAS  Google Scholar 

  • Villeda-Hernandez J, Barroso-Moguel R, Mendez-Armenta M, Nava-Ruiz C, Huerta-Romero R, Rios C (2001) Enhanced brain regional lipid peroxidation in developing rats exposed to low level lead acetate. Brain Res Bull 55(2):247–251

    Article  CAS  PubMed  Google Scholar 

  • 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 154:654–656

    Article  PubMed  Google Scholar 

  • Yang LP, Keam SJ, Keating GM (2007) Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs 67(15):2211–2230

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to S. J. Fatemi.

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Balooch, F.D., Fatemi, S.J. & Iranmanesh, M. Combined chelation of lead (II) by deferasirox and deferiprone in rats as biological model. Biometals 27, 89–95 (2014). https://doi.org/10.1007/s10534-013-9689-0

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  • DOI: https://doi.org/10.1007/s10534-013-9689-0

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