The interaction mechanisms of toxic metal ions with the dimercaprol drug and cellulose chain have not yet been fully elucidated. The interactions between M[2+](H2O)4-6 ions (M = Zn, Cd, and Hg) and the thiol groups of thioalcohols as well as the hydroxy groups of alcohols were investigated using the M06-2X functional. The effects of the aqueous solvent were evaluated using the solvation model based on density (SMD). The two-layer ONIOM approach and molecular electrostatic potential (MEP) maps were employed for the hydroxyl groups of linear cellulose. The affinity of Zn[2+](H2O)4-5 ions toward the dimercaprol molecule was probed at the M06-2X/6-311+G** level of theory. Furthermore, calculations using the B3LYP and B3LYP-D3BJ functionals were performed for comparison. The calculated results indicated that the adjacent dissociation Gibbs free energy changes (ΔrG[0]) of the metal complexes depend significantly on the inductive effects of substituent R, the molecular volume, the length of the linear cellulose, the chelation effect, and the hardness or softness of complexing elements. The affinity of M[2+](H2O)5 ions toward the sixth water molecule and methanol molecule decreases in the order of Zn[2+] > Cd[2+] > Hg[2+], whereas the reverse trend is observed for the methanethiol molecule. The C-O and C-S bond lengths in the metal complexes are longer than those of the free ligands. The computational results were in good agreement with the experimental data and with the hard and soft acids and bases (HSAB) theory.

Lead encephalopathy is a rare but life-threatening neurotoxic emergency in children. Although rare, lead encephalopathy can mimic infectious encephalitis leading to delay in diagnosis and management in resource-limited settings. A toddler belonging to poor socioeconomic strata presented with non-bilious vomiting for 6 days, intermittent fever for 3 days, seizures and rapidly deteriorating neurological status a few hours prior to arrival in triage. A thorough history later found the child's visits to a battery recycling unit. Blood lead levels (BLL) were 88.1 mcg/dL. Chelation therapy with intramuscular dimercaprol (British anti-Lewisite) along with calcium disodium EDTA was administered via intramuscular injection for 5 days but the child deteriorated due to severe brain herniation, resulting in demise. In cases of unexplained encephalopathy in children (after ruling out infectious causes) along with the presence of environmental and occupational risk factors with biochemical support, lead toxicity must be considered early. Early targeted history taking and chelation are essential to prevent irreversible damage.

Objective: To investigate the clinical efficacy of combined hemoperfusion (HP) and continuous veno-venous hemodialysis filtration (CVVHDF) in tandem therapy together with sodium dimercaptopropanesulfonate (DMPS) for patients with acute organotin poisoning, and to analyze the effects of this combined regimen on clinical symptoms, serum tin levels, urinary tin levels, and serum potassium levels. Methods: In December 2023, the clinical data of four patients with acute organotin poisoning were retrospectively analyzed. All patients received comprehensive symptomatic supportive therapy, DMPS-based tin removal therapy, and HP+CVVHDF tandem blood purification therapy. Changes in clinical symptoms, serum tin levels, urinary tin levels, and serum potassium levels were compared before and after treatment. Results: Prior to treatment, the serum tin levels of the four patients ranged from 192.8 to 366.5 μg/L, and urinary tin levels ranged from 1203.1 to 2419.2 μg/L; all patients exhibited hypokalemia with serum potassium levels ranging from 2.60 to 2.90 mmol/L. After combined therapy, serum tin levels decreased to 1.0-4.2 μg/L, urinary tin levels decreased to 4.1-16.0 μg/L, and serum potassium levels recovered to 3.9-4.1 mmol/L, with electrolyte disturbances corrected. Neurological symptoms such as coma, convulsions, and psychiatric abnormalities, as well as metabolic acidosis, significantly improved or resolved completely within 3-20 days after treatment, and all four patients recovered and were discharged. Conclusion: The combined HP+CVVHDF tandem blood purification therapy with DMPS and comprehensive symptomatic supportive therapy effectively eliminates organotin from the body, corrects electrolyte and acid-base imbalances, and alleviates neurological symptoms, demonstrating clinical applicability.

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.

The design of specific inhibitors of metallo-β-lactamases (MBL) is one of the priority research lines due to the spread of carbapenem resistant bacterial strains which limits therapeutic options. In parallel, the investigation of new uses of known medicines is prompted by regulatory agencies. In this work, the potential MBL inhibitory potency of L-captopril (an antihypertensive drug) and dimercaprol (used in poisoning by metals) was investigated in a clinical collection of Enterobacterales and Pseudomonas spp. In addition, a comprehensive review of the available literature was conducted, to discuss jointly new and previously available data. The results indicate that activity of imipenem and meropenem combined with 400 mg/l is restored for > 80% and 60%, respectively, for Enterobacterales strains, but not in the Pseudomonas group. Dimercaprol had a limited activity in both bacterial groups. Based on these promising results of L-captopril, pharmacological calculations were performed. It is concluded that the repurposing objective could not be achieved as the overall data indicated that the concentrations of captopril required to achieve carbapenemase inhibitory activity in vivo are higher than maximum used in treatment. Communication of negative results would help to discontinue active current research on L-captopril and should focus on other potential MBL inhibitors.

Iron overload significantly contributes to chronic kidney disease progression by triggering oxidative stress and mitochondrial impairment via the Fenton reaction. This study investigates the protective role of aldehyde dehydrogenase 1a3 (ALDH1a3), an enzyme that detoxifies reactive aldehydes, in renal iron overload. C57BL/6N mice were fed a 2.25% ferric citrate diet for 24 weeks to establish a chronic model, followed by treatment with the chelator Dimercaprol (DP). In vitro, TCMK-1 cells were subjected to iron intervention with ALDH1a3 overexpression or inhibition. Chronic iron overload induced significant renal iron deposition, lipid peroxidation (elevated MDA, depleted GSH), and mitochondrial structural damage. ALDH1a3 was endogenously upregulated in renal tubular epithelial cells under iron stress. Overexpressing ALDH1a3 significantly enhanced cell viability, suppressed reactive oxygen species and MDA levels, and preserved mitochondrial membrane potential, whereas its inhibition exacerbated cellular damage. Furthermore, DP treatment reduced iron deposition and was associated with increased ALDH1a3 expression. In conclusion, ALDH1a3 acts as a critical endogenous protective factor against iron-induced nephrotoxicity by mitigating oxidative damage and maintaining mitochondrial stability. These findings indicate that ALDH1a3 is a promising potential therapeutic target for the treatment of iron overload-related kidney diseases.

Infantile elemental mercury poisoning is clinically rare and poses a severe long-term health threat. This report describes a rare case of non-accidental infantile elemental mercury poisoning, in which the infant was continuously exposed to mercury vapor for 20 days starting from postnatal day 15. The infant initially presented with feeding difficulties and respiratory symptoms, which rapidly progressed to respiratory distress and seizure-like episodes at 5 months of age; laboratory tests revealed severe hypoglycemia and metabolic acidosis. Despite 5 days of intravenous glucose infusion and comprehensive support involving mechanical ventilation, sedation, and corticosteroids, hypoglycemia and epileptic symptoms persisted. The diagnosis of mercury poisoning was confirmed by a blood mercury test and governmental investigation, followed by two courses of dimercaptopropane sulfonate (DMPS) chelation therapy, after which hypoglycemia, respiratory symptoms, and epilepsy were effectively managed. The patient was discharged 25 days after admission. CT images revealed no abnormalities in the head at admission, but subsequent MRI at discharge and thereafter indicated persistent brain damage, including signal abnormalities and cerebral atrophy. This case suggests that severe hypoglycemia can be a critical component of infantile elemental mercury poisoning and contributes to persistent neurological injury. It also highlights that the efficacy of chelation therapy is severely limited when treatment is delayed after prolonged exposure. Current chelators such as DMPS have poor blood-brain barrier penetration and cannot effectively remove accumulated inorganic mercury from the CNS, underscoring the urgent need for novel CNS-penetrating therapeutic strategies in delayed presentations.

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.

Acrolein is a highly reactive α,β-unsaturated aldehyde produced endogenously through lipid peroxidation and enzymatic metabolism and exogenously via environmental exposures. Acrolein covalently adducts to DNA and proteins, leading to oxidative stress, mitochondrial dysfunction, and inflammation, including innate immune response activation via natural antibodies. Acrolein is difficult to measure in biological systems, but its covalent products can be measured reliably. Therapeutically, nucleophilic small molecules that scavenge acrolein such as hydralazine, phenelzine, dimercaprol, carnosine, and N-acetylcysteine (NAC) have shown neuroprotective effects in animal models of multiple sclerosis, Parkinson's disease, spinal cord injury, and traumatic brain injury. These effects include preserved membrane and mitochondrial integrity, reduced inflammation, reduced pain, and improved motor, sensory, and cognitive outcomes. Alternative strategies that enhance clearance or inhibit production of acrolein show promise but face limitations. Acrolein is a key pathophysiological mediator and a viable therapeutic target in central nervous system trauma and neurodegenerative diseases.

Lead (Pb) is recognized as one of the most prevalent metals found in the Earth's crust. Its affordability and easy accessibility have led to its extensive use in various industrial applications. Over recent decades, the global issue of heavy metal pollution has escalated, despite increased awareness. This situation is particularly concerning in developing nations, where Pb toxicity poses a significant threat to public health. A critical challenge in addressing Pb toxicity lies in its diagnosis, as it often presents asymptomatically, with many symptoms overlapping with other medical conditions. Blood Pb levels (BLLs) serve as a primary diagnostic test, while additional screening methods assess hematological alteration, including the breakdown of RBCs, elevated coproporphyrin levels, zinc protoporphyrin, and urinary porphyrins, among others. This review intends to outline the systemic toxicity of Pb, emphasizing its impact on various systems, including the Respiratory, Hematological, Nervous, Cardiovascular, Hepatic, Renal, Skeletal, and Reproductive systems. Additionally, this article also examines its genotoxic effect and associated cancer risks. Consequently, there is an urgent need to investigate alternative prevention strategies against Pb toxicity, particularly through dietary supplementation. This review focuses on the vital role of dietary supplements in mitigating Pb toxicity and highlights advanced management approaches. It thoroughly examines the protective effects of phytochemicals, vitamins, probiotics, essential metals, edible plants, and other nutritional supplements in combating Pb toxicity. Furthermore, it discusses advanced chelation therapies utilizing various chelating agents such as CaNa2EDTA, DMPS, succimer, D-penicillamine, and dimercaprol in a dedicated section. The findings of the present review work indicate that incorporating nutrient supplements into regular diet plans is both straightforward and cost-effective, with fewer side effects compared to alternative treatments. Therefore, these protective strategies are deemed effective and beneficial in reducing the impact of Pb toxicity.

Snakebite envenoming causes more than 130,000 deaths and more than 400,000 disabilities per year and has been classified as a priority Neglected Tropical Disease by the World Health Organization (WHO). While antivenom therapy remains the mainstay of snakebite treatment, small molecule therapeutics (SMTs) have been proposed as potential adjuncts to antivenom, particularly as oral treatment in the prehospital setting. Several SMTs have demonstrated efficacy in preclinical models of snakebite envenoming, with varespladib, a secreted phospholipase A2 (sPLA2) inhibitor, being granted orphan drug status for its potential to treat snakebite. The present study investigated the potential of four SMTs (e.g., varespladib, marimastat, nafamostat and dimercaprol) to neutralise toxic components present in the venom of southern African snake species. In vitro experimentation found that varespladib potently inhibited snake venom phospholipase A2 (svPLA2) activity in Bitis arietans (IC50 = 0.221 μM) and B. gabonica (IC50 = 0.276 μM). Marimastat exhibited potent inhibition of snake venom metalloproteinase (svMP) in several snake species with IC50 values ranging from 0.0042 to 3.06 μM, while dimercaprol, a metal chelator, was a lower potency svMP inhibitor with IC50 values ranging from 5.01 to 79.8 μM. Nafamostat proved to be an inhibitor of snake venom serine protease (svSP) in B. arietans (IC50 = 3.72 μM), B. gabonica (IC50 = 3.80 μM) and Causus rhombeatus (IC50 = 0.261 μM). These data demonstrate that SMTs are effective inhibitors of the relevant enzymes in several snake species and support the proposal that SMTs could be developed for therapeutic intervention in snakebite envenoming.

Two children aged <5 years presented with paraesthesias, limb pain, behavioural disturbances, weight loss and poor sleep for 2.5 months and had hypertension on examination.Extensive evaluation for aetiologies of hypertension, including catecholamine-secreting and neural crest tumours, cardiac, endocrine and renal causes, was inconclusive.History subsequently revealed the use of alternative Indian medicine in both children. Heavy metal toxicity was suspected and was confirmed with elevated 24-hour urinary mercury levels. Both children responded well to chelation therapy with dimercaprol and had resolution of symptoms on follow-up.These two cases highlight that heavy metal toxicity in children is an evolving health concern of global importance. Hence, knowledge about the presence of heavy metals as an ingredient in some alternative medicines, seeking history about their usage and suspecting the varied clinical manifestations of heavy metal toxicity is essential while evaluating a child with uncontrolled hypertension.