Chelation therapy in lead poisoning: pharmacological mechanisms, clinical applications and emerging therapeutic approaches

Background: Lead poisoning remains a significant global public health concern because of its widespread environmental distribution, occupational exposure and persistent toxic effects on multiple organ systems. Lead is a cumulative toxic metal that primarily affects the nervous, haematological, renal, cardiovascular and reproductive systems. Children are particularly vulnerable because of their developing nervous systems and greater gastrointestinal absorption of lead. Although prevention and elimination of exposure are the primary approaches to management, chelation therapy plays an important role in patients with significantly elevated blood lead concentrations or severe clinical manifestations. Objective: This review examines the pharmacological mechanisms of chelation therapy in lead poisoning, evaluates the clinical applications and limitations of currently available chelating agents, and discusses emerging therapeutic approaches and future research directions. Methods: A narrative literature review was developed using published scientific literature, clinical studies, toxicological reviews and international clinical guidelines. Particular emphasis was placed on the pharmacodynamics, pharmacokinetics, therapeutic efficacy, safety profiles and clinical applications of dimercaprol, calcium disodium EDTA, succimer and D-penicillamine. Results: Chelating agents reduce the biologically available lead burden by forming stable metal–ligand complexes that facilitate elimination, predominantly through renal excretion. Succimer is commonly used in selected patients with moderate lead poisoning, whereas calcium disodium EDTA and dimercaprol have important applications in severe poisoning and lead encephalopathy. However, clinical evidence indicates that reducing blood lead concentrations does not necessarily reverse established neurological injury. The Treatment of Lead-Exposed Children (TLC) trial demonstrated that succimer reduced blood lead concentrations in children with moderately elevated levels but did not improve long-term neuropsychological development. Emerging approaches include improved chelator design, targeted metal-binding molecules, antioxidant adjuncts, nanotechnology-based delivery systems and interventions directed towards oxidative stress and mitochondrial dysfunction. Conclusion: Chelation therapy remains an essential intervention for selected cases of lead poisoning, but its effectiveness depends on appropriate patient selection, removal of the exposure source, pharmacological characteristics of the chelating agent and careful clinical monitoring. Future research should focus on developing safer and more selective chelators capable of reducing tissue lead burden while minimizing essential mineral depletion and neurological complications