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Title: In-vitro/in-vivo correlation of the nature of excreted species after chelation therapy with 2,3-dimercaptopropane-1-sulfonic acid
Author: Al-Mahasneh, Qusai M.
ISNI:       0000 0001 3406 8730
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2001
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Treatment of lead poisoning relies primarily on chelation therapy. The sodium salt of (R,S)-2,3-dimercapto-l-propanesulfonic acid (DMPS, DimavalL ®) is a water-soluble analogue of British Anti-Lewisite (BAL). Its oral dosage form is considered effective for the diagnosis and treatment of mercury poisoning (Aposhian et a!., 1995). In adults, therapeutically successful attempts have been reported for the treatment of chronic lead poisoning with DMPS (Anatovskaya, 1962). In children having chronic lead poisoning, the efficacy of DMPS was noted following a 5-day therapy (Chisholm & Thomas, 1985). Despite its current use in chelation therapy for the treatment of lead poisoning, detailed chemical characterization and/or investigation of the resulting complexes has not been fully investigated. DMPS and its complexes with lead are electro active, consequently have been investigated using electro analytical techniques. This present work was designed with the aim of (a) investigating the in-vitro complexing behavior of DMPS with lead at simulated physiological conditions, (b) in-vivo investigation of the chelation therapy of low and highly exposed subjects (workers). Electroanalytical techniques including: Voltammetry at the Dropping Mercury electrode, Differential Pulse Polarography (DPP), Anodic Stripping Voltammetry (ASV), and Cathodic Stripping Voltammetry (CSV), have been employed for investigating the complexing properties ofDMPS. Application of the methods suggested by Deford-Hume and ShumanWoodward for measuring stability constants of metal complexes, showed that the formed Pb:DMPS complex could be a labile coordination complex having a formation constant ofKf= 2.66xI04 • In addition, the results demonstrated that the Pb:DMPS species was much weaker than that formed between Pb2 + and EDTA (Kf = 1.25xI018 ). This may indicate that the mobilized lead from soft tissues and bone after chelation may have involved mechanisms other than complex formation. The in-vitro results demonstrated that electroanalytical techniques proved to be highly sensitive and selective for investigating both lead as well as DMPS levels in biological fluids. However, after chelation optimizing the media to enhance selectivity was necessary. Upon titration of DMPS versus lead or alternatively lead versus DMPS, the results showed that lead did not form a stable coordination complex. However, a compound with enough stability was formed which mobilized lead from body stores as demonstrated by levels of lead in urine measured after a single oral dose of DMPS (100 mg/ 3 capsules). Additionally, after dosing of exposed subjects classified as having low and high lead body burden, in-vivo findings showed that lead was substantially chelated after dosing with 100 mg DMPS/ 3 capsules. However, the lead-DMPS complex was not detected in urine and hence was regarded as a labile coordination complex. The latter finding compared well with in-vitro studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry Biochemistry Pharmacology