Unit 11: Chelation Therapy

• Heavy-metal poisoning


  Accumulation of toxic metal in the body, mainly in the soft tissue
• Metals considered heavy metals


  • Lead
  • Mercury
  • Arsenic
  • Thallium
  • Cadmium
  • Zinc
  • Copper
  • Chromium
  • Iron
  • Manganese
• How heavy metals are taken up


  • Ingestion (food or drink)
  • Inhalation
  • Absorption through skin
• Heavy metals


  Compete with essential metals for receptors, leading to organ damage
• Symptoms of heavy-metal poisoning


  • Vomiting, nausea, diarrhoea, sweating, headache, metallic taste in mouth
  • Impairment of cognitive, motor and language skills
• Diagnosing heavy-metal poisoning


  • Blood and urine tests
  • Hair, tissue and X-ray analysis
• Chelation therapy


  Binding of toxic heavy metal to a chelating agent, reducing toxicity and removing it from the body
• Chelation


  Binding of molecules to a metal ion, forming more than one bond
• Chelating ligands


  Organic compounds that can form more than one bond to the metal ion
• Denticity


  Number of bonds a ligand can form to a metal ion
• Chelating agents used in heavy-metal poisoning treatment


  • Dimercaprol (BAL)
  • Calcium disodium edetate
  • Penicillamine
  • Succimer (DMSA)
  • Unithiol (DMPS)
  • α-Lipoic acid (ALA)
• Chelation therapy mechanism


  1. Chelating agent binds to metal in body tissues

  2. Complex travels in bloodstream

  3. Complex filtered by kidneys and excreted in urine
• Common chelating agents used in the treatment of heavy-metal poisoning

  • Dimercaprol (BAL, British anti-Lewisite)
  • Calcium disodium edetate
  • Penicillamine
• Succimer (DMSA, meso-2,3-dimercaptosuccinic acid)


  Unlicensed drug that may be valuable in the treatment of most forms of heavy-metal poisoning including lead, arsenic and mercury
• Other chelating agents used in alternative medicine


  • Unithiol (DMPS, 2,3-dimercapto-1-propanesulfonic acid)
  • a-lipoic acid (ALA)
• No medical study has proven the effectiveness of chelation therapy for any clinical application other than heavy-metal poisoning
• Mode of action of chelating agents


  1. Bind to the metal in the body's tissues and form a chelate

  2. Complex is released from the tissue and travels in the bloodstream

  3. Complex is filtered by the kidneys and excreted in the urine
• Chelation therapy requires admission to the hospital because it may be painful and it is important to stabilise the vital functions of the patient
• The patient may require treatment for complications associated with heavy-metal poisoning, including anaemia and kidney failure or shock reactions
• Chelation therapy


  • Especially effective treatment option for poisoning with lead, mercury and arsenic
  • Very difficult to treat cadmium poisoning, no really effective therapy found so far
• Calcium disodium edetate


  Also referred to as calcium sodium EDTA, a synthetic amino acid that can bind to metals via the four carboxylate and two amine groups
• Metals that edetate forms specially strong complexes with

  • Co(III)
  • Cu(II)
  • Mn(II)
  • Fe(III)
• Edetate

  Indicated for the treatment of lead poisoning, especially a problem for navy personnel after World War II
• Side effects of edetate include nausea, diarrhoea and abdominal pain, and it can lead to renal damage if given as overdosage
• Edetate is typically administered by intravenous infusion for up to 5 days
• Other clinical applications of edetate


  • Chromium-EDTA can be used to evaluate kidney function, administered intravenously and its filtration into the urine is monitored
  • EDTA and its salts can act as an anticoagulant for blood samples and is often found as additives in blood sampling bottles
• Dimercaprol (BAL)


  • Chelating agent used as an antidote for arsenic, antimony, bismuth, gold and mercury poisoning
  • Developed by British scientists at the University of Oxford during World War II as an antidote to Lewisite, an arsenic-based chemical warfare agent
• Mode of action of BAL


  Contains sulfhydryl groups and competes with enzymes for the coordination of the metal, the chelated complex is then excreted in the urine
• BAL increases the concentration of some metals in the human body and therefore limits its use, not indicated as an antidote for cadmium, selenium or iron poisoning
• BAL is very toxic and has only a narrow therapeutic window, with multiple side effects including hypertension, malaise, tachycardia, nausea, diarrhoea, burning sensation and muscle pain
• BAL is administered by intramuscular injection and is fairly painful, formulated with peanut oil as solvent due to its instability in water
• Dimercaptosuccinic acid (DMSA)


  • Modification of BAL containing two thiol groups and two carboxylic acid groups, also known as Succimer
  • Developed in the 1960s and replaced BAL and edetate in some countries for the treatment of lead, arsenic and mercury poisoning
• 2,3-Dimercapto-1-propanesulfonic acid (DMPS)


  Thiol-containing chelating agent with an additional sulfate group, found to be a useful chelating agent and have some effect as an antidote to mercury
• Lipoic acid (ALA)


  • Also known as a-lipoic acid or thioctic acid, contains a disulfide group that can be transformed in the body to a dithiol group
  • On the market since the 1950s as a dietary supplement, a natural antioxidant usually made by the body
  • Researchers in the former Soviet Union found that ALA can chelate mercury once it is transformed into the dithiol-containing compound
  • Can penetrate both the blood-brain barrier and the cell membrane, but there is much debate about its mode of action, side effects and effectiveness, other antidotes like BAL and DMSA are more efficient in the removal of heavy metals