The Scientific Basis for Chelation: Animal Studies and Lead Chelation

Abstract

This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating agents to children who do not have elevated tissue lead levels. It is of significant concern that this type of therapy has been advocated for treating autism.

The management of embedded metal fragment patients and the role of chelation Therapy: A workshop of the Department of Veterans Affairs—Walter Reed National Medical Center

“…However, when the source of metal exposure is from tissue‐embedded metal fragments, additional challenges and patient risks arise in locating, and if medically indicated, removing the fragments 15 . While there is a relatively large body of evidence from human and animal model studies on chelation treatment of metal poisoning (primarily lead) from oral or respiratory exposures, 43 there is limited evidence of chelation efficacy in the treatment of patients with embedded metal fragments. Several studies on chelation in animal models of human lead poisoning were therefore reviewed with the goal of informing management options for chelation in patients with embedded fragments and to identify key knowledge gaps that should be filled.…”

“…exposures, 43 there is limited evidence of chelation efficacy in the treatment of patients with embedded metal fragments. Several studies on chelation in animal models of human lead poisoning were therefore reviewed with the goal of informing management options for chelation in patients with embedded fragments and to identify key knowledge gaps that should be filled.…”

Medical Countermeasures—Chelation Therapy

“…However, there are many reports regarding its effectiveness and low toxicity in the treatment of arsenic in the Soviet and Chinese literature [27]. Smith and Strupp [65] reported the efficacy and clinical utility of DMSA in rodents and non-human studies. It may be given parenterally or orally in doses of 30 mg/kg/day for 5-7 days followed by 20 mg/kg/day for 1-3 weeks; it is rapidly excreted in urine.…”

Medical Toxicology Case Presentations: to Chelate or Not to Chelate, Is that the Question?

“…Serial BLL testing was also useful in assessment of the adequacy of exposure source identification and removal. As discussed elsewhere in this issue, the impact of chelation treatment on BLL decline can also be tracked, although correlation is lacking to clinical or subclinical improvement [4,5]. & The role for chelation therapy:…”

“…In particular, one of the symposium presenters, Dr. Donald Smith, noted that much of the recrudescent blood lead (even in children) comes from bone mobilization [7]. This makes the decision to chelate a given BLL even more problematic in view of redistributing lead from bone versus reducing brain exposure to lead [4,5]. & Information or systemic issues to reduce confusion or error and improve future care: Following identification of this case, an Epi-X report was filed.…”