Chelation in metal intoxication

Abstract

Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

Keywords: antioxidant; chelating agents; combination therapy; heavy metals; monoesters; oxidative stress; succimer.

Figure 1.

Formation of metal ligand complexes using mono, bi and polydentate ligands.

Figure 2.

Characteristics of an ideal chelating agent for better chelation of heavy metals.

Figure 3.

Structures of two different complexes of metals with chelating agents. (A) Stable complex prevent interaction of metal with bio-molecules, (B) Basket complex enhance interaction of metal with bio-molecules. Symbols used: B- Bio-molecules; C-Chelating agent; M-Metal.

Figure 4.

Structures of various chelating agents used to treat cases of heavy metal poisoning.

Figure 5.

Chemical reaction of lewisite with British Anti Lewisite (BAL) to give a stable 5-membered ring complex.

Figure 6.

Limitations of DMSA in the treatment of mercury toxicity.

Figure 7.

Newly synthesized monoesters of DMSA.

Figure 8.

Benefits and drawbacks of chelation therapy.

Figure 9.

Beneficial effects of combination therapy.

Figure 10.

Acute and chronic exposure symptoms of metal toxicity and possible preventive and therapeutic measures against them.

Figure 11.

showing possible mechanism involved for the better therapeutic efficacy of combined chelation therapy in lead/arsenic poisoning using two different chelating agents.