Chemistry, Pharmacology, and Toxicology of Monoisoamyl Dimercaptosuccinic Acid: A Chelating Agent for Chronic Metal Poisoning

Abstract

Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.

Toward a Mechanism-Driven Integrated Framework to Link Human Exposure to Multiple Toxic Metal(loid) Species with Environmental Diseases

“…While orally- or intravenously-administered chelating agents can be an effective strategy to treat As III , Cd 2+ , Hg 2+ and Pb 2+ exposed individuals [ 128 ], adverse effects of chelation therapy frequently occur [ 129 ]. Thus, more effective chelating agents that offer fewer side effects continue to be developed [ 130 , 131 ]. Recent results, which involved N-acetyl-L-cysteine (NAC), provided important new insight into the mobilization of CH 3 Hg + from tissues.…”

Antidotes in Clinical Toxicology—Critical Review

“…It has been used since the 1950s. It is a lipophilic chelator and, therefore, is also a chelating agent for other divalent metals such as mercury, arsenic, cadmium, and gallium arsenide [ 43 ]. It is an organic sulphur compound with two sulfhydryl groups with the formula C 4 H 6 O 4 S 2 .…”

Mercuric Chloride Induced Nephrotoxicity: Ameliorative Effect of Carica papaya Leaves Confirmed by Histopathology, Immunohistochemistry, and Gene Expression Studies

“…19 Although many studies have confirmed heavy-metal-induced oxidative stress, the usefulness of antioxidants along with chelation therapy has not been extensively investigated. 20 Traditionally, medicinal plants have always been used as the primary constituent for the remedy of various illnesses. Recently, India and countries around the globe have used alternative medicines and medicinal herbs, and their bioactive compounds are familiar because they cure various kinds of illnesses by synchronizing with the body's immune system.…”

“…Although many studies have confirmed heavy-metal-induced oxidative stress, the usefulness of antioxidants along with chelation therapy has not been extensively investigated. 20 …”