Dimercaprol 100mg/2ml solution for injection ampoules

This study analyzes the activities, poisoning, and medical treatment of the "La Esperanza" mercury mine workers in Aranzazu (Caldas, Colombia) between 1948 and 1975. The mining work there was difficult due to the geological instability of the area and the use of inappropriate mining technology, which generated a high occurrence of poisoning manifested in tremors of limbs, bleeding gums, loss of teeth, and bad mouth odor. The mine was the first Colombian company to treat its poisoned workers with dimercaprol and penicillamine. Occupational toxicology in Colombia was thus born during one of the most significant occupational health disasters in the country.

Abstract licence: CC BY

IntroductionAcute copper toxicity is a rare occurrence, and management guidelines are not based on robust evidence. Treatment recommendations are often extrapolated from those of chronic copper intoxication and the management of Wilson's disease. Although D-penicillamine, EDTA, and dimercaprol have varying success, we describe the use of chelation with succimer monotherapy in a patient with acute copper salt ingestion with subsequent improvement of clinical status and copper concentrations.Case reportA 38-year-old woman presented to an ED after ingestion of liquid copper fungicide containing 27.5% copper diammonia diacetate complex. The regional poison center initially recommended D-penicillamine along with supportive care. Due to the lack of availability of D-penicillamine, succimer was chosen as an alternative agent. The patient developed mild hemolysis and liver injury during her stay, but did not develop any kidney injury. She had a Zargar 2A caustic injury to the stomach and duodenal bulb. She received succimer for a total of 10 days, and copper concentrations decreased from 1,295 mcg/dL (reference range: 80-158 mcg/dL) to normal levels before discharge.DiscussionThere is limited evidence surrounding chelation therapy in acute copper poisoning. We describe a case of a patient who clinically improved while receiving aggressive supportive care and associated succimer monotherapy after acute ingestion of a copper compound.

Abstract licence: CC BY

Gut disorders are largely caused by iron-induced microbial dysbiosis. Excess iron disrupts barrier integrity by inducing oxidative stress, leading to impaired cellular processes. The determination of therapeutic compounds that can reduce iron-induced damage and maintain gut cellular integrity is still a top objective. Dimercaprol (DP) represents a novel iron-chelating strategy for the treatment of iron-induced gut disorders. A chronic iron-overload model was established in mice via intragastric gavage of ferric citrate (FC) (286 mg/kg BW) for 16 weeks. Similarly, IPEC-J2 cells were exposed to FC (50 µmol/L) for 24 h. DP was used as a mechanistic probe to elucidate the pathways involved in iron-induced toxicity. Cells were transfected with or without NRF2 siRNA and exposed to DP post-FC. Colonic contents were assessed via metagenomics and metabolomics. Both in vivo and in vitro experiments were analyzed through a multifaceted analysis, Western blot, RT-qPCR, ELISA, transmission electron microscopy and immunofluorescence assays. Thiols in DP protect gut cells from damage by boosting their natural antioxidant defenses via the NRF2/HO-1 pathway. The DP mechanism of action is multifaceted, including enhancement of barrier integrity, protecting mitochondrial structure and function, suppression of inflammation and endoplasmic reticulum (ER) stress and restoration of gut microbial and metabolic homeostasis. These protective effects are mainly caused by the activation of the NRF2/HO-1 pathway, which makes DP a potential therapeutic agent for disorders caused by chronic gut injury induced by FC. DP provides strong protection against iron-induced gut damage by restoring organelle crosstalk, redox homeostasis and microbial–metabolic balance through NRF2/HO-1 signaling.

Abstract licence: CC BY 4.0

Dimercaprol (British antilewisite, BAL) is a long-established chelating agent used in the treatment of heavy metal poisoning; however, its physicochemical and thermochemical properties have not yet been fully characterized. In this study, we combined gas-phase quantum chemical calculations with high-resolution mass spectrometry to investigate the conformational stability, fragmentation pathways, and thermochemical parameters of BAL. Fragmentation behavior was examined by gas chromatography/mass spectrometry-QTOF under electronic ionization conditions, and the resulting spectra were interpreted through proposed dissociation pathways involving water, hydrogen sulfide, and thiyl radical losses, supported by reaction enthalpies calculated at the theoretical level M06-2X/6-311++G(3df,3pd). Conformational analysis identified five low-energy structures (BAL-1 to BAL-5), where intramolecular hydrogen bonds and gauche/anti interactions play a key role in stability; BAL-3 was consistently predicted as the lowest-energy conformer. Vibrational frequencies calculated with the B3LYP, M06-2X, and MN15 functionals showed good agreement with experimental FTIR and Raman data. The thermochemical properties were further evaluated using Gn composite methods (G3MP2B3, G3B3, G4MP2 and G4) which yielded an average standard enthalpy of formation at ΔH°(f,298K) of -45.6 ± 1.1 kcal/mol. This work provides a detailed experimental and theoretical characterization of dimercaprol, providing information on its possible fragmentation mechanism and conformational landscape, and offering a thermochemical framework that could support future pharmacological, toxicological and environmental applications.

Abstract licence: CC BY 4.0