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Metal Poisoning and Chelation Therapy

Year 2024, Volume: 2 Issue: 3, 126 - 131, 30.10.2024

Pınar Buluz , Nuri Başpınar

https://doi.org/10.61845/agrimedical.1503465

Abstract

Despite more than half a century of clinical experience, chelation for toxic heavy metals remains one of the most controversial and misapplied interventions in clinical toxicology. There is sufficient evidence that the proper use of specific chelates, when combined with general supportive care, reduces the morbidity and mortality associated with serious poisonings. In this review, we provide an update on available chelation agents and treatment strategies for the treatment of five heavy metal (mercury, lead, arsenic, cadmium, copper) intoxications.

Keywords

metal chelation mercury copper lead Cadmiyum arsenic

References

  • 1. Kim JJ, Kim YS, Kumar V. Heavy metal toxicity: An update of chelating therapeutic strategies. J Trace Elem Med Biol. 2019;54:226-231.
  • 2. Gürtunca Ş. Metal Şelatları. Ankara Üniv Vet Fak Derg. 1968;15(02):271-279.
  • 3. Blanusa M, Varnai VM, Piasek M, Kostial K. Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771–2794.
  • 4. Martín J, Alés M, Asuero A. An overview on ligands of therapeutically interest. Pharm Pharmacol Int J. 2018;6(3):198-214.
  • 5. Risher JF, Nickle RA, Amler SN. Elemental mercury poisoning in occupational and residential settings: two case studies. Int J Hyg Environ Health. 2003;206:371–379.
  • 6. Hultberg B, Anderson A, Isaksson A. Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol. Toxicology.2001;156(2-3):93–100.
  • 7. Kozikowska I, Binkowski LJ, Szczepanska K, et al. Mercury concentrations in human placenta, umbilical cord, cord blood and amniotic fluid and their relations with body parameters of newborns. Environ. Pollut. 2013;182:256–262 (Barking, Essex:1987).
  • 8. Aaseth J, Skaug MA, Cao Y, Andersen O. Chelation in metal intoxication—Principles and paradigms. J Trace Elem Med Biol. 2015;31:260–266.
  • 9. Qin AB, Liu L, Gao BX, Su TA. Case of chronic mercury poisoning associated nephrotic syndrome, abdominal pain, and neuropsychiatric symptoms. Ren Fail. 2023;45(2):2261553.
  • 10. Devoto P, Flore G, Ibba, A, Fratta, W, Pani, L. Lead intoxication during intrauterine life and lactation but not during adulthood reduces nucleus accumbens dopamine release as studied by brain microdialysis. Toxicol Lett. 2001;121(3):199-206.
  • 11. Kalita J, Kumar V, Misra UK, Bora HK. Memory and learning dysfunction following copper toxicity: biochemical and immunohistochemical basis. Mol Neurobiol. 2018;55(5):3800–3811.
  • 12. Flora SJ, Flora G, Saxena G, Mishra M. Arsenic and lead induced free radical generation and their reversibility following chelation. Cell Mol Biol (Noisy-le-Grand). 2007;53(1):26–47.
  • 13. Gracia RC, Snodgrass WR. Lead toxicity and chelation therapy. Am J Health Syst Pharm.2007;64(1):45–53.
  • 14. Alfares H, Rafsanzani RA, Mansyur M. Examining the Chelating Effectiveness of Dimercaptosuccinic Acid and Ethylenediaminetetraacetic acid Calcium Disodium in Patients with Lead Poisoning: An Evidence-Based Case Report. Occup Environ Med J Indonesia. 2023; 1(2): 6.
  • 15. Hans Wedepohl K. The composition of the continental crust. GCA Acta. 1995;59(7):1217–1232.
  • 16. Nordberg GF, Nogawa K, Nordberg M, Friberg L. Cadmium. In: Gunnar F. Nordberg, Bruce A. Fowler et al. eds. Handbook of the Toxicology of Metals, 3th ed. Elsevier; 2007:445–486.
  • 17. Abernethy DR, DeStefano AJ, Cecil TL, Zaidi K, Williams RL. Metal impurities in food and drugs. Pharma Res. 2010;27(5):750–755.
  • 18. Bernhof RA. Cadmium Toxicity and Treatment. Review Article. Los Angeles, CA 93023, USA. Hind Publis Corp Sci World J. 2013; 7.
  • 19. Schauder A, Avital A, Malik Z. Regulation and gene expression of heme synthesis under heavy metal exposure— review. J Environ Pathol Toxicol Oncol. 2010;29(2):137–158.
  • 20. Fujiwara Y, Lee JY, Tokumoto M. Cadmium renal toxicity via apoptotic pathways. Biol Pharm Bull. 2012;35(11):1892–1897.
  • 21. Abu-Hayyeh S, Sian M, Jones KG, Manuel A, Powell JT. Cadmium accumulation in aortas of smokers Arterioscler Thromb Vasc Biol. 2001;21(5):863–867.
  • 22. Edwards JR, Prozialeck WC. Cadmium, diabetes and chronic kidney disease. Toxicol Appl Pharmacol. 2009;238(3):289–293.
  • 23. Gallagher CM, Meliker JR. Blood and urine cadmium, blood pressure, and hypertension: a systematic review and meta-analysis. Environ Health Perspect. 2010;118(12):1676–1684.
  • 24. Horiguchi H, Oguma E, Kayama F. Cadmium induces anemia through interdependent progress of hemolysis, body iron accumulation, and insufficient erythropoietin production in rats. Toxicol Sci. 2011;122(1):198–210.
  • 25. Ferramola ML, Perez Diaz MF, Honore SM. Cadmium-induced oxidative stress and histological damage in the myocardium.Toxicol Appl Pharmacol. 2012;265(3):380–389.
  • 26. Johnson MD, Kenney N, Stoica A. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med. 2003;9(8):1081–1084.
  • 27. Cheng CY, Mruk DD. The blood-testis barrier and its implications for male contraception. Pharmacol Rev. 2012;64(1):16–64.
  • 28. McCarty MF. Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure, Med Hypotheses. 2012;79(5):642–648.
  • 29. Satarug S, Moore MR. Emerging roles of cadmium and heme oxygenase in type-2 diabetes and cancer susceptibility. Tohoku J Exp Med. 2012;228(4):267–288.
  • 30. Shagirtha K, Muthumani M, and Prabu SM. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur Rev Med Pharmacol Sci. 2011;15(9):1039–1050.
  • 31. Shargorodsky J, Curhan SG, Henderson E. Heavy metals exposure and hearing loss in US adolescents Arch Otolaryngol Head Neck Surg. 2011;137(12):1183–1189.
  • 32. Czarnecki LA, Moberly AH, Turkel DJ. Functional rehabilitation of cadmium-induced neurotoxicity despite persistent peripheral pathophysiology in the olfactory system. Toxicoll Sci. 2012;126(2):534–544.
  • 33. Vasken Aposhian H. Biological chelation: 2,3-dimercaptoprop anesulfonicacid and mesodimercaptosuccinic acid. Adv Enzyme Regul. 1982;20:301–319.
  • 34. Waters RS, Bryden NA, Patterson KY, Veillon C, and Anderson RA. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res. 2001;83(3):207–221.
  • 35. Bamonti F, Fulgenzi A, Novembrino C. Metal chelation therapy in rheumathoid arthritis: a case report. Successful management of rheumathoid arthritis by metal chelation therapy. Biometals. 2011;24(6):1093–1098.
  • 36. Gil HW, Kang EJ, Lee KH, Yang JO, Lee EY, Hong SY. Effect of glutathione on the cadmium chelation of EDTA in a patient with cadmium intoxication. Hum Exp Toxicol. 2011;30(1):79–83.
  • 37. Olaolu T, Jibulu F, Damilare R. Hepatotoxic effect of cadmium and available therapeutic options. Thai J Pharm Sci. 2023;46(6):631-637.
  • 38. Mohammed BA, Lawal B, Oshevire DB, et al. Arsenic poisoning: the risk, clinical features and treatment. Bio J Sci Tec Res. 2020;31(1):23884-23890.
  • 39. Prakash S, Verma AK. Arsenic: it's toxicity and impact on human health. Int J Biol Inn, IJBI. 2021;3(1):38-47.
  • 40. Das M, Singh KK, Khan E, et al. N-Acetylcysteine versus arsenic poisoning: A mechanistic study of complexation by molecular spectroscopy and density functional theory. J mol liquids. 2021; 340:117168.
  • 41. Hordyjewska A, Popiolek L, Kocot J. The many “faces” of copper in medicine and treatment. Biometals. 2014;27(4):611–621.
  • 42. Palumaa P. Metabolism of copper and possibilities for its regulation. Proceedings Estonian Academy Sci. 2023;72(4):382–392.
  • 43. Srinivasan P, Madheswaran R, Kumar RS, et al. Spontaneously Occurring Chronic Copper Toxicosis in Pattanam Breed of Sheep. Ind J Animal Res. 2024;58(2):253-258.
  • 44. Santini C, Pellei M, Gandin V. Advances in copper complexes as anticancer agents. Chem Rev. 2014;114(1):815–862.
  • 45. Brown OC, Baguña Torres J, Holt KB. Copper complexes with dissymmetrically substituted bis(thiosemicarbazone) ligands as a basis for PET radiopharmaceuticals: control of redox potential and lipophilicity. Dalton Trans. 2017;46(42):14612–14630.
  • 46. Djoko KY, Goytia MM, Donnelly PS. Copper(II)- bis(tiosemicarbazonato) complexes as antibacterial agents: insights into their mode of action and potential as therapeutics. Antimicrob Agents Chemother. 2015;59(10):6444–6453.
  • 47. Kostova I. Toxic metals and antidotes. J Clin Images Med Case Rep. 2023;4(1):2240.
  • 48. Kobylarz D, Noga M, Frydrych A, Milan J, Morawiec A, Glaca A, Jurowski K. Antidotes in Clinical Toxicology—Critical Review. Toxics. 2023;11(9):723.
  • 49. Pillay V. Current views on antidotal therapy in managing cases of poisoning and overdose. JAPI. 2008;56:881-892.

Metal Zehirlenmeleri ve Şelasyon Tedavisi

Year 2024, Volume: 2 Issue: 3, 126 - 131, 30.10.2024

Pınar Buluz , Nuri Başpınar

https://doi.org/10.61845/agrimedical.1503465

Abstract

Yarım yüzyıldan fazla süren klinik deneyime rağmen, toksik ağır metallere yönelik şelasyon, klinik toksikolojide en tartışmalı ve yanlış uygulanan müdahalelerden biridir. Spesifik şelatların doğru kullanımının genel destekleyici bakımla birleştirildiğinde ciddi zehirlenmelerle ilişkili morbidite ve mortaliteyi azalttığına dair yeterli kanıt vardır. Bu derlemede, beş ağır metal (civa, kurşun, arsenik, kadmiyum, bakır) intoksikasyonunun tedavisi için mevcut şelasyon ajanları ve tedavi stratejileri hakkında bir güncelleme sunuyoruz.

Keywords

metal zehirlenme civa arseik kurşun kadmiyum bakır şelasyon

References

  • 1. Kim JJ, Kim YS, Kumar V. Heavy metal toxicity: An update of chelating therapeutic strategies. J Trace Elem Med Biol. 2019;54:226-231.
  • 2. Gürtunca Ş. Metal Şelatları. Ankara Üniv Vet Fak Derg. 1968;15(02):271-279.
  • 3. Blanusa M, Varnai VM, Piasek M, Kostial K. Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771–2794.
  • 4. Martín J, Alés M, Asuero A. An overview on ligands of therapeutically interest. Pharm Pharmacol Int J. 2018;6(3):198-214.
  • 5. Risher JF, Nickle RA, Amler SN. Elemental mercury poisoning in occupational and residential settings: two case studies. Int J Hyg Environ Health. 2003;206:371–379.
  • 6. Hultberg B, Anderson A, Isaksson A. Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol. Toxicology.2001;156(2-3):93–100.
  • 7. Kozikowska I, Binkowski LJ, Szczepanska K, et al. Mercury concentrations in human placenta, umbilical cord, cord blood and amniotic fluid and their relations with body parameters of newborns. Environ. Pollut. 2013;182:256–262 (Barking, Essex:1987).
  • 8. Aaseth J, Skaug MA, Cao Y, Andersen O. Chelation in metal intoxication—Principles and paradigms. J Trace Elem Med Biol. 2015;31:260–266.
  • 9. Qin AB, Liu L, Gao BX, Su TA. Case of chronic mercury poisoning associated nephrotic syndrome, abdominal pain, and neuropsychiatric symptoms. Ren Fail. 2023;45(2):2261553.
  • 10. Devoto P, Flore G, Ibba, A, Fratta, W, Pani, L. Lead intoxication during intrauterine life and lactation but not during adulthood reduces nucleus accumbens dopamine release as studied by brain microdialysis. Toxicol Lett. 2001;121(3):199-206.
  • 11. Kalita J, Kumar V, Misra UK, Bora HK. Memory and learning dysfunction following copper toxicity: biochemical and immunohistochemical basis. Mol Neurobiol. 2018;55(5):3800–3811.
  • 12. Flora SJ, Flora G, Saxena G, Mishra M. Arsenic and lead induced free radical generation and their reversibility following chelation. Cell Mol Biol (Noisy-le-Grand). 2007;53(1):26–47.
  • 13. Gracia RC, Snodgrass WR. Lead toxicity and chelation therapy. Am J Health Syst Pharm.2007;64(1):45–53.
  • 14. Alfares H, Rafsanzani RA, Mansyur M. Examining the Chelating Effectiveness of Dimercaptosuccinic Acid and Ethylenediaminetetraacetic acid Calcium Disodium in Patients with Lead Poisoning: An Evidence-Based Case Report. Occup Environ Med J Indonesia. 2023; 1(2): 6.
  • 15. Hans Wedepohl K. The composition of the continental crust. GCA Acta. 1995;59(7):1217–1232.
  • 16. Nordberg GF, Nogawa K, Nordberg M, Friberg L. Cadmium. In: Gunnar F. Nordberg, Bruce A. Fowler et al. eds. Handbook of the Toxicology of Metals, 3th ed. Elsevier; 2007:445–486.
  • 17. Abernethy DR, DeStefano AJ, Cecil TL, Zaidi K, Williams RL. Metal impurities in food and drugs. Pharma Res. 2010;27(5):750–755.
  • 18. Bernhof RA. Cadmium Toxicity and Treatment. Review Article. Los Angeles, CA 93023, USA. Hind Publis Corp Sci World J. 2013; 7.
  • 19. Schauder A, Avital A, Malik Z. Regulation and gene expression of heme synthesis under heavy metal exposure— review. J Environ Pathol Toxicol Oncol. 2010;29(2):137–158.
  • 20. Fujiwara Y, Lee JY, Tokumoto M. Cadmium renal toxicity via apoptotic pathways. Biol Pharm Bull. 2012;35(11):1892–1897.
  • 21. Abu-Hayyeh S, Sian M, Jones KG, Manuel A, Powell JT. Cadmium accumulation in aortas of smokers Arterioscler Thromb Vasc Biol. 2001;21(5):863–867.
  • 22. Edwards JR, Prozialeck WC. Cadmium, diabetes and chronic kidney disease. Toxicol Appl Pharmacol. 2009;238(3):289–293.
  • 23. Gallagher CM, Meliker JR. Blood and urine cadmium, blood pressure, and hypertension: a systematic review and meta-analysis. Environ Health Perspect. 2010;118(12):1676–1684.
  • 24. Horiguchi H, Oguma E, Kayama F. Cadmium induces anemia through interdependent progress of hemolysis, body iron accumulation, and insufficient erythropoietin production in rats. Toxicol Sci. 2011;122(1):198–210.
  • 25. Ferramola ML, Perez Diaz MF, Honore SM. Cadmium-induced oxidative stress and histological damage in the myocardium.Toxicol Appl Pharmacol. 2012;265(3):380–389.
  • 26. Johnson MD, Kenney N, Stoica A. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med. 2003;9(8):1081–1084.
  • 27. Cheng CY, Mruk DD. The blood-testis barrier and its implications for male contraception. Pharmacol Rev. 2012;64(1):16–64.
  • 28. McCarty MF. Zinc and multi-mineral supplementation should mitigate the pathogenic impact of cadmium exposure, Med Hypotheses. 2012;79(5):642–648.
  • 29. Satarug S, Moore MR. Emerging roles of cadmium and heme oxygenase in type-2 diabetes and cancer susceptibility. Tohoku J Exp Med. 2012;228(4):267–288.
  • 30. Shagirtha K, Muthumani M, and Prabu SM. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur Rev Med Pharmacol Sci. 2011;15(9):1039–1050.
  • 31. Shargorodsky J, Curhan SG, Henderson E. Heavy metals exposure and hearing loss in US adolescents Arch Otolaryngol Head Neck Surg. 2011;137(12):1183–1189.
  • 32. Czarnecki LA, Moberly AH, Turkel DJ. Functional rehabilitation of cadmium-induced neurotoxicity despite persistent peripheral pathophysiology in the olfactory system. Toxicoll Sci. 2012;126(2):534–544.
  • 33. Vasken Aposhian H. Biological chelation: 2,3-dimercaptoprop anesulfonicacid and mesodimercaptosuccinic acid. Adv Enzyme Regul. 1982;20:301–319.
  • 34. Waters RS, Bryden NA, Patterson KY, Veillon C, and Anderson RA. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res. 2001;83(3):207–221.
  • 35. Bamonti F, Fulgenzi A, Novembrino C. Metal chelation therapy in rheumathoid arthritis: a case report. Successful management of rheumathoid arthritis by metal chelation therapy. Biometals. 2011;24(6):1093–1098.
  • 36. Gil HW, Kang EJ, Lee KH, Yang JO, Lee EY, Hong SY. Effect of glutathione on the cadmium chelation of EDTA in a patient with cadmium intoxication. Hum Exp Toxicol. 2011;30(1):79–83.
  • 37. Olaolu T, Jibulu F, Damilare R. Hepatotoxic effect of cadmium and available therapeutic options. Thai J Pharm Sci. 2023;46(6):631-637.
  • 38. Mohammed BA, Lawal B, Oshevire DB, et al. Arsenic poisoning: the risk, clinical features and treatment. Bio J Sci Tec Res. 2020;31(1):23884-23890.
  • 39. Prakash S, Verma AK. Arsenic: it's toxicity and impact on human health. Int J Biol Inn, IJBI. 2021;3(1):38-47.
  • 40. Das M, Singh KK, Khan E, et al. N-Acetylcysteine versus arsenic poisoning: A mechanistic study of complexation by molecular spectroscopy and density functional theory. J mol liquids. 2021; 340:117168.
  • 41. Hordyjewska A, Popiolek L, Kocot J. The many “faces” of copper in medicine and treatment. Biometals. 2014;27(4):611–621.
  • 42. Palumaa P. Metabolism of copper and possibilities for its regulation. Proceedings Estonian Academy Sci. 2023;72(4):382–392.
  • 43. Srinivasan P, Madheswaran R, Kumar RS, et al. Spontaneously Occurring Chronic Copper Toxicosis in Pattanam Breed of Sheep. Ind J Animal Res. 2024;58(2):253-258.
  • 44. Santini C, Pellei M, Gandin V. Advances in copper complexes as anticancer agents. Chem Rev. 2014;114(1):815–862.
  • 45. Brown OC, Baguña Torres J, Holt KB. Copper complexes with dissymmetrically substituted bis(thiosemicarbazone) ligands as a basis for PET radiopharmaceuticals: control of redox potential and lipophilicity. Dalton Trans. 2017;46(42):14612–14630.
  • 46. Djoko KY, Goytia MM, Donnelly PS. Copper(II)- bis(tiosemicarbazonato) complexes as antibacterial agents: insights into their mode of action and potential as therapeutics. Antimicrob Agents Chemother. 2015;59(10):6444–6453.
  • 47. Kostova I. Toxic metals and antidotes. J Clin Images Med Case Rep. 2023;4(1):2240.
  • 48. Kobylarz D, Noga M, Frydrych A, Milan J, Morawiec A, Glaca A, Jurowski K. Antidotes in Clinical Toxicology—Critical Review. Toxics. 2023;11(9):723.
  • 49. Pillay V. Current views on antidotal therapy in managing cases of poisoning and overdose. JAPI. 2008;56:881-892.
There are 49 citations in total.

Details

Primary Language Turkish
Subjects Biochemistry and Cell Biology (Other)
Journal Section Review Article
Authors

Pınar Buluz 0009-0007-9110-4428

Nuri Başpınar 0000-0002-5481-1111

Publication Date October 30, 2024
Submission Date June 22, 2024
Acceptance Date October 7, 2024
Published in Issue Year 2024 Volume: 2 Issue: 3

Cite

AMA Buluz P, Başpınar N. Metal Zehirlenmeleri ve Şelasyon Tedavisi. Ağrı Med J. October 2024;2(3):126-131. doi:10.61845/agrimedical.1503465
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