RARE DISEASE
Cyanide poisoning
Cyanide poisoning
Cyanide poisoning
Drug discovery
12
drugs
With orphan designations
Overview
Cyanide poisoning rapidly disrupts cellular oxygen utilization by inhibiting cytochrome c oxidase, leading to histotoxic hypoxia [12][17]. Acute exposure causes dizziness, tachypnea, vomiting, seizures, and cardiovascular collapse, often with lactic acidosis >8 mmol/L [3][6]. Diagnosis relies on clinical context and labs; treatment requires immediate hydroxocobalamin (first-line) or sodium thiosulfate with nitrites, plus airway/hemodynamic support [8][13]. Chronic low-dose exposure from cassava consumption causes neurological sequelae like konzo [2][15].
Therapies
Antidotes: Hydroxocobalamin (5g IV) preferred for safety; sodium thiosulfate (12.5g IV) augments detoxification [3][8][13]
Supportive care: 100% oxygen, mechanical ventilation, and sodium bicarbonate for acidosis [6][17]
Contraindications: Avoid nitrites in smoke-inhalation patients with carboxyhemoglobinemia [8][14]
Categories: rare disorders due to toxic effects
Research Papers
951 drug discovery papers about Cyanide poisoning, with 12 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
951 drug discovery papers about Cyanide poisoning, with 12 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-23 | Tunable and self-reporting esterase-activated cyanide prodrugs exert cytoprotective effects.
Hydrogen cyanide (HCN) is increasingly recognized as a mammalian gasotransmitter with biphasic biological effects, but its study is limited by the lack of controllable delivery tools. Here we report esterase-activated, self-reporting cyanide donors with tunable release kinetics and fluorogenic readout. Upon esterase activation, the donors synchronously release cyanide and regenerate an ICT-based fluorophore. Steric modulation at the cyanohydrin α-carbon controls the release rate over one order of magnitude (kobs = 0.04-0.83 min-1). In cell-based assays, biological outcomes correlate with cyanide generation rate rather than nominal donor concentration, producing proliferation at low rates and toxicity at higher rates. Cytoprotection occurs within an experimentally observed range of 0.3-0.7 nmol mg-1 protein h-1 under these conditions. In the MCAO model, the lead donor Et-1 administered at 1 μmol kg-1 (0.3 mg kg-1) reduces infarct volume and attenuates lipid peroxidation and inflammation.
2026-07-12 | Deadly Greens: Understanding Cyanide (Sorghum) Poisoning in Cattle
Cyanide poisoning, also referred to as prussic acid or hydrocyanic acid poisoning, is a serious toxic condition in cattle and represents a significant concern for dairy farmers. It commonly occurs when cattle graze on young sorghum shoots, which naturally contain cyanogenic compounds capable of releasing cyanide. Once absorbed, cyanide disrupts cellular respiration by preventing cells from utilizing oxygen, resulting in rapid tissue damage and cell death. The condition is particularly common in ruminants and is characterized by its acute onset and high fatality rate. In many cases, affected animals are found dead without prior warning, although signs such as difficulty breathing, muscle tremors, and bright red or congested mucous membranes may be observed before death. Due to its rapid action and severe consequences, cyanide poisoning remains an important health and management challenge in cattle production.
2026-06-30 | Case Report: Successful multimodal management of a lethal cyanide poisoning - insights into the role of early blood purification and potential bedside monitoring indicators.
This article reports a rare and lethal case of cyanide poisoning, aiming to explore its early diagnosis and successful treatment strategies. Upon admission, the patient presented with cardiac and respiratory arrest, deep coma, and severe metabolic acidosis. The core resuscitation measures included early mechanical ventilation, vasoactive drug support, bicarbonate therapy, and the early initiation of continuous blood purification as part of a multimodal strategy. We observed that a combination of elevated central venous partial pressure of carbon dioxide (PvCO2) and elevated lactate provided potential bedside clues for early suspicion of cyanide poisoning. During treatment, a rise in PvCO2 accompanied by a decrease in lactate was noted, which may serve as a hypothesis-generating observation for treatment response, acknowledging the influence of multiple concurrent interventions. The patient recovered substantially after comprehensive treatment. This case provides valuable experience for the treatment of cyanide poisoning.
2026-06-07 | Cobalamin (Vitamin B12) in Clinical Practice: Indications, Molecular Mechanisms, and Management of Deficiency
Cobalamin (vitamin B12) is an essential micronutrient and a potent pharmacological agent with well-established roles in DNA synthesis, myelin maintenance, and cellular metabolism. This scholarly review provides a comprehensive, clinically oriented analysis of cobalamin’s indications, mechanisms of action, pharmacokinetics, adverse effect profiles, contraindications, and monitoring parameters. The discussion distinguishes between FDA-approved indications—including pernicious anemia, atrophic gastritis, chronic acid suppression, metformin use, gastrectomy, small bowel bacterial overgrowth, Diphyllobothrium latum infection, pancreatic insufficiency, and dietary deficiency—and off-label uses such as cyanide poisoning and vasoplegia. Emphasis is placed on the dual cofactor functions of cobalamin in the methionine synthase and methylmalonyl-CoA mutase pathways, explaining the pathophysiological consequences of deficiency, including megaloblastic anemia and subacute combined degeneration of the spinal cord. The review critically compares oral versus parenteral administration, highlighting the clinical utility of high-dose oral cobalamin even in intrinsic factor deficiency. Monitoring strategies, including reticulocyte response, normalization of methylmalonic acid and homocysteine, and vigilance for hypokalemia or thrombocytosis, are outlined. Importantly, this review underscores the necessity of an interprofessional team approach—integrating clinicians, pharmacists, nurses, dietitians, and specialists—to achieve optimal patient outcomes. No significant toxicity is associated with cobalamin, but hypersensitivity, Leber optic nerve atrophy, and drug interactions require careful consideration. Ultimately, this activity aims to equip healthcare professionals with the conceptual and practical tools to diagnose, treat, and manage cobalamin deficiency effectively across diverse clinical contexts.
2026-06-02 | A pilot study in the swine model of lethal cyanide intoxication indicates efficacy of a platinum-methionine complex countermeasure.
Cyanide presents a chemical security threat because of its wide availability, due to industrial uses, and significant toxicity. Platinum-thioether complexes are a recent addition to candidate antidotes, showing efficacy in mouse models of hydrogen cyanide inhalation and reversing toxicity measures in rabbits. This pilot study evaluated the effectiveness of a platinum-methionine complex (Met2Pt), a potent lead candidate, in a lethal swine model, which provides a solid foundation for future research. Potassium cyanide (0.2 mg/kg/min; IV) was infused into anesthetized swine until 6 min post-apnea. Met2Pt (2.9 mg Pt/kg in 3 mL) or 100 mM phosphate buffer vehicle (3 mL) were then administered intravenously (IV) or intramuscularly (IM). Vital signs, metabolites, and pharmacokinetics were monitored for > 90 min. IV Met2Pt was highly efficacious compared to all other treatments, rescuing all swine in the group and reversing cyanide-derangements in lactate concentration (Welch One-Way ANOVA, p < 10- 4), blood oxygenation (p = 0.002), etc. IM Met2Pt did not significantly improve survival due to lower systemic availability (7%). The results of this pilot study indicate that Met2Pt is efficacious via the IV route, while IM availability of Met2Pt is a limiting factor.
proteins
2026-08-19 | Evaluation of PEGylated Methemoglobin for Sequestration of Cyanide, Azide, and Sulfide in In Vitro Binding Models.
Cyanide, azide, and sulfide are potent inhibitors of mitochondrial enzymes that disrupt cellular energy metabolism and can cause rapid, potentially fatal outcomes. Effective treatments for these toxic anions remain limited, underscoring the need for broadly acting antidotal strategies. Methemoglobin (methHb), the ferric form of hemoglobin (hHb), binds these ligands with high affinity and acts as a mechanistic scavenger by sequestering toxic anions before they can interact with mitochondrial targets. PEGylation of methHb (met-PEG-hHb) offers a strategy to improve methHb molecular stability and may reduce potential oxidative side effects while altering protein interactions that could influence future in vivo pharmacokinetic behavior. In this study, we characterize various met-PEG-hHbs as multiligand scavengers using in vitro binding models. Size-exclusion high-performance liquid chromatography (SEC-HPLC) and dynamic light scattering (DLS) confirm that PEGylation preserves molecular size and homogeneity after oxidation, while circular dichroism spectroscopy demonstrates maintenance of protein secondary structure. UV-vis spectroscopy and stopped-flow kinetics reveal that met-PEG-hHb rapidly and efficiently binds cyanide, azide, and sulfide. These findings show that PEGylation stabilizes methHb while preserving its ability to bind cyanide, azide, and sulfide in vitro, supporting met-PEG-hHb as a promising platform for further preclinical evaluation as a broad-spectrum toxic anion scavenger.
2026-02-24 | Evaluation of methemoglobin and polymerized methemoglobin for detoxification of cyanide, azide, and sulfide in in vitro binding models.
Cyanide, azide, and sulfide are fast-acting cellular poisons that inhibit mitochondrial respiration by targeting metal centers within key enzymes, leading to rapid energy failure and potentially lethal metabolic collapse. Despite their clinical relevance, specific antidotes capable of broadly neutralizing these toxic anions remain limited. Methemoglobin (methHb), the ferric form of hemoglobin with high affinity for these ligands, has been recognized as a mechanistic antidote capable of sequestering toxic anions before they reach mitochondrial targets. Polymerized hemoglobin (PolyhHb) and its oxidized counterpart, polymerized methemoglobin (metPolyhHb), offer a promising strategy to potentially enhance the stability, circulation time, and safety profile of methHb-based detoxification systems. In this study, we characterize methHb and metPolyhHb as multi-ligand scavengers using in vitro binding models. High-performance liquid chromatography (HPLC) and dynamic light scattering (DLS) demonstrated that oxidation of PolyhHb does not alter its molecular size or distribution. Circular dichroism confirmed preservation of secondary structure following oxidation. Using UV-visible spectroscopy and stopped-flow kinetics, we show that both methHb and metPolyhHb rapidly and efficiently bind cyanide, azide, and sulfide. These findings demonstrate that PolyhHb retains structural integrity upon oxidation and maintains strong detoxification capability across multiple toxic anions, supporting its potential as a versatile platform for broad-spectrum antidotal development.
2025-12-10 | NirA is a Cyanide-Tolerant Nitrite Reductase Which Protects Pseudomonas aeruginosa From Self-Poisoning.
Host production of nitric oxide in response to P. aeruginosa results in accumulation of nitrite and nitrate at the infection site, with both utilised for anaerobic respiration to support survival. Nitric oxide and nitrite also act as aerobic respiratory inhibitors. P. aeruginosa must overcome these toxic metabolites alongside self-produced cyanide to persist at the infection site. We previously identified a novel nitrite reductase (NirA) that supports P. aeruginosa virulence in a wide range of infection models. In this work, we demonstrate that mutation of nirA inhibits growth of P. aeruginosa at reduced oxygen tensions in the presence of nitrite or nitrate, with this phenotype shown to be dependent on cyanide. NirA is a siroheme-dependent enzyme, a classical target for inhibition with cyanide. Biochemical characterisation confirms that NirA is a novel cyanide-tolerant nitrite reductase, which supports reduction of nitrite in the presence of cyanide. We hypothesise that NirA enables detoxification of nitrite to prevent build-up of multiple respiratory inhibitors and facilitate cyanide-resistant aerobic respiration at low oxygen tensions. Through targeting effectors of these resistance mechanisms, we could promote P. aeruginosa self-poisoning and prevent adaptation to the reduced oxygen environment typically encountered by P. aeruginosa in biofilms and during infection.
2024-08-13 | Characterization of rhodanese synthesized by the wild and EMS-mutated Klebsiella oxytoca JCM1665
Cyanide poisoning remains a significant concern for both civilian and military personnel worldwide. Rhodanese, a cyanide detoxify enzyme produced by the wild (KOJCM1665) and two selected mutant strains (KOJCM1665c and KOJCM1665d) of Klebsiella oxytoca JCM 1665 was purified and characterized using a combination of standard techniques. Extracellular rhodanese yield of the wild and selected mutants were 6.2 ± 0.6, 26.7 ± 0.7 and 18.3 ± 0.3 U/mL respectively. The overall levels of recovery of rhodanese activity and fold after purification were 49 %, 66 %, and 58 % and 2.6, 2.6, and 2.3 % for the wild, KOJCM 1665c, and KOJCM 1665d, respectively. The native molecular weights of the three enzyme preparations were 35.1, 34.9, and 34.8 kDa, while the subunit molecular weight was 35 kDa for all the enzymes. The optimum activity of the enzymes was observed at 50 °C and pH 6.0. The real km of the three enzyme preparations for KCN as a substrate were 1.03 × 10−3, 0.95 × 10−3, and 0.80 × 10−3 M, respectively, while the km for the second substrate (Na2S2O3) were 0.59 × 10−3, 0.49 × 10−3, and 0.69 × 10−3 M, respectively. The substrate specificity study showed that the enzyme preferred sodium thiosulfate as the substrate. Metal ions such as Na+ and K+ had significantly greater inhibitory effects on enzyme activity. This study demonstrated the potential of enhancing K. oxytoca JCM 1665 to overexpress extracellular rhodanese, and the physicochemical properties of the enzyme hold significant promise as a target for improving the efficiency of cyanide bioremediation processes.
2023-12-16 | Elucidating the binding properties of methemoglobin in red blood cell to cyanide, hydrosulfide, and azide ions using artificial red blood cell.
Methemoglobin (metHb), the oxidized form of hemoglobin, lacks the ability of reversible oxygen binding; however, it has a high binding affinity to toxic substances such as cyanide, hydrosulfide, and azide. This innate property of metHb offers the clinical option to treat patients poisoned with these toxins, by oxidizing the endogenous hemoglobin in the red blood cells (RBCs). The binding properties of naked metHb (isolated from RBC) with these toxins has been studied; however, the binding behaviors of metHb under the intracellular conditions of RBC are unclear because of the difficulty in detecting metHb status changes in RBC. This study aimed to elucidate the binding properties of metHb in RBC under physiological and poisoned conditions using artificial RBC, which was hemoglobin encapsulated in a liposome. The mimic-circumstances of metHb in RBC (metHb-V) was prepared by oxidizing the hemoglobin in artificial RBC. Spectroscopic analysis indicated that the metHb in metHb-V exhibited a binding behavior different from that of naked metHb, depending on the toxic substance: When the pH decreased, (i) the cyanide binding affinity of metHb-V remained unchanged, but that of naked metHb decreased (ii) the hydrosulfide binding affinity was increased in metHb-V but was decreased in naked metHb. (iii) Azide binding was increased in metHb-V, which was similar to that in naked metHb, irrespective of the pH change. Thus, the binding behavior of intracellular metHb in the RBC with cyanide, hydrosulfide, and azide under physiological and pathological conditions were partly elucidated using the oxidized artificial RBC.
cell therapies
2025-07-25 | Potential of some lactic acid bacteria inoculants in the bioremediation of cyanogenic glycosides in sorghum straw silage
Sorghum is a vital economic crop in China, generating substantial amounts of crop residues annually, which necessitates research into its comprehensive utilization. Cyanogenic glycosides, a class of metabolites widely distributed in sorghum and other plant species, tend to release hydrogen cyanide under enzymatic action, posing a potential poisoning risk to animals. In the present study, to enhance the fermentation quality of sorghum straw silage, β-glucosidase-producing lactic acid bacteria isolated from fresh sorghum straw were employed as inoculants. A systematic investigation was conducted on the microbial community structure and metabolomic profiles following 60 days of fermentation, utilizing untargeted metabolomics analysis to elucidate the mechanisms by which β-glucosidase-producing lactic acid bacteria influence sorghum straw silage fermentation quality, as well as the degradation of dhurrin and reduction of hydrocyanic acid levels in sorghum. The results demonstrated that the silage fermentation quality in the lactic acid bacteria-supplemented experimental group was significantly improved compared to the control group. Attributed to the modulation of metabolic pathways, the levels of dhurrin and hydrocyanic acid exhibited a significant decrease with extended ensiling duration. At the metabolite level, biological pathways involved in steroid biosynthesis, terpenoid synthesis, and carotenoid synthesis were upregulated during different stages of ensiling. These metabolites not only enhance the nutritional value of the feed, but also possess anti-inflammatory and health-promoting properties, thereby further underscoring the positive regulatory role of lactic acid bacteria in the silage process.
2024-10-09 | Detoxification of hydrocyanide by fermentation of apricot seeds with probiotic Lactobacillus strains isolated from breast milk
Many plants produce substances known as cyanogenic glycosides, which, when hydrolyzed, can release hydrogen cyanide. These include apricot (Prunus armeniaca L.) seeds, the subject of the study presented here. Amygdalin when metabolized, turns into hydrocyanide, which can cause cyanide poisoning if ingested in large quantities. The current study used Lactobacillus spp. that were isolated from breast milk. High concentrations of hydrocyanic acid, which apricot seeds contain, are dangerous during fermentation by Lactobacillus spp. The aim of the present study is to recognize the most effective methods for detoxifying apricot seeds and fermented amygdalin extract, while conserving or enhancing the physical properties, chemical structure, minerals and amino acids. Activation of bacterial isolates was followed by fermentation. Next a cellular cytotoxicity test for extract was conducted. After fermentation, we evaluated the cytotoxic effect on cancer and normal cell in vitro. After fermentation, a detoxification of apricot seeds was shown resulting from the presence of compound and improvement of vitamins formed due to fermentation. The use of Lactobacillus bacteria isolated from breast milk resulted in the production of a new fermented milk product containing aqueous extract of apricot seeds free from life-threatening toxicity. Fermentation produced a new probiotic with less toxic hydrocyanide, fatty acid, and amino acid, showing cytotoxic effects on cancer cells and minimal toxicity to normal cells.
2023-08-16 | The isolation of rumen enterococci strains along with high potential utilizing cyanide.
Cyanogenic glycosides in forage species and the possibility of cyanide (CN) poisoning can have undesirable effects on ruminants. The literature estimates that unknown rumen bacteria with rhodanese activity are key factors in the animal detoxification of cyanogenic glycosides, as they are capable of transforming CN into the less toxic thiocyanate. Therefore, identifying these bacteria will enhance our understanding of how to improve animal health with this natural CN detoxification process. In this study, a rhodanese activity screening assay revealed 6 of 44 candidate rumen bacterial strains isolated from domestic buffalo, dairy cattle, and beef cattle, each with a different colony morphology. These strains were identified as belonging to the species Enterococcus faecium and E. gallinarum by 16S ribosomal DNA sequence analysis. A CN-thiocyanate transformation assay showed that the thiocyanate formation capacity of the strains after a 12 h incubation ranged from 4.42 to 25.49 mg hydrogen CN equivalent/L. In addition, thiocyanate degradation resulted in the production of ammonia nitrogen and acetic acid in different strains. This study showed that certain strains of enterococci substantially contribute to CN metabolism in ruminants. Our results may serve as a starting point for research aimed at improving ruminant production systems in relation to CN metabolism.
2023-03-17 | CRISPR-Cas9-mediated knockout of CYP79D1 and CYP79D2 in cassava attenuates toxic cyanogen production
Cassava (Manihot esculenta) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces the neurotoxin cyanide and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. This problem is further exacerbated by drought conditions which increase this toxin in the plant. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444; the West African, farmer-preferred cultivar TME 419; and the improved variety TMS 91/02324. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. The congruence of results across accessions indicates that our approach could readily be extended to other preferred or improved cultivars. This work demonstrates cassava genome editing for enhanced food safety and reduced processing burden, against the backdrop of a changing climate.
2022-09-28 | Whole-genome analysis guided molecular mechanism of cyanogenic glucoside degradation by yeast isolated from Prunus mume fruit syrup.
Consumption of fermented Prunus mume fruit (maesil) sugar syrup raise a health concern due to the presence of the cyanogenic glucoside amygdalin. The goal of the present study was to investigate the amygdalin degradation potential and genome profile of the native microbes found in maesil syrup. The microbial profile analysis revealed that yeast is the predominant microorganism native to maesil syrup and that the isolated yeast cells showed a remarkable potential for amygdalin reduction (99.7%). Moreover, the reduction in amygdalin was inversely proportional to the growth of the isolated yeast. The whole-genome analysis revealed that the isolated yeast is Zygosaccharomyces rouxii (genome size 10 Mb, 39.25% of GC content). Of the 5250 genes (64.88%) predicted in the Z. rouxii genome, 5245 (99.90%) were annotated using NCBI Non-Redundant, UniProt, and InterProScan databases. The genome of the isolated Z. ruoxii harbored 2.03% of repeats and 0.68% of non-coding RNAs. Protein prediction indicated that β-glycosidases and hydroxynitrile lyase may play a key role in amygdalin degradation. The predicted degradation initiated by β-glycosidases that hydrolyze α-glucosidic bonds of amygdalin results in α-hydroxy nitriles (cyanohydrins) that are subsequently converted into carbonyl compounds (benzaldehyde) and hydrogen cyanide catalyzed by hydroxynitrile lyases. Present findings provide valuable data for constructing engineered microorganisms that can degrade amygdalin. Further analysis of Z. rouxii may elucidate the exact mechanism of amygdalin reduction in the production of maesil syrup.
gene therapies
2025-12-12 | Sorghum Poisoning in Livestock: Mechanisms, Risks, and Sustainable Mitigation Strategies
Sorghum (Sorghum bicolor L. Moench) is a vital drought-tolerant crop cultivated in arid and semi-arid regions, serving as both food and fodder. However, under environmental stress, sorghum accumulates cyanogenic glucosides (primarily dhurrin), which hydrolyze into toxic hydrogen cyanide (HCN) upon ingestion, posing lethal risks to livestock. This review examines the biochemical pathways of dhurrin synthesis and HCN release, highlighting key risk factors including drought, frost, and improper grazing management. This study is structured to first elucidate the biochemical and risk factors behind sorghum poisoning, then to evaluate a suite of integrated mitigation strategies—from agroforestry to genetic solutions—and finally to discuss the implementation pathways through education and policy.We evaluate mitigation strategies such as agroforestry integration—using nitrogen-fixing trees (Leucaena leucocephala, Gliricidia sepium) to reduce plant stress and provide alternative fodder—alongside feed management techniques (ensiling, sulfur supplementation). Additionally, we explore genetic solutions (low-dhurrin cultivars developed via CRISPR-Cas9) and microbial/phytoremediation approaches (Pseudomonas fluorescens, Eucalyptus camaldulensis) for cyanide detoxification. Farmer education on risk recognition and safe practices emerges as a critical preventive measure. By synthesizing current research, this paper proposes integrated, sustainable strategies to minimize sorghum poisoning while maintaining agricultural productivity in vulnerable regions.
small molecules
2026-09-23 | Tunable and self-reporting esterase-activated cyanide prodrugs exert cytoprotective effects.
Hydrogen cyanide (HCN) is increasingly recognized as a mammalian gasotransmitter with biphasic biological effects, but its study is limited by the lack of controllable delivery tools. Here we report esterase-activated, self-reporting cyanide donors with tunable release kinetics and fluorogenic readout. Upon esterase activation, the donors synchronously release cyanide and regenerate an ICT-based fluorophore. Steric modulation at the cyanohydrin α-carbon controls the release rate over one order of magnitude (kobs = 0.04-0.83 min-1). In cell-based assays, biological outcomes correlate with cyanide generation rate rather than nominal donor concentration, producing proliferation at low rates and toxicity at higher rates. Cytoprotection occurs within an experimentally observed range of 0.3-0.7 nmol mg-1 protein h-1 under these conditions. In the MCAO model, the lead donor Et-1 administered at 1 μmol kg-1 (0.3 mg kg-1) reduces infarct volume and attenuates lipid peroxidation and inflammation.
2026-07-12 | Deadly Greens: Understanding Cyanide (Sorghum) Poisoning in Cattle
Cyanide poisoning, also referred to as prussic acid or hydrocyanic acid poisoning, is a serious toxic condition in cattle and represents a significant concern for dairy farmers. It commonly occurs when cattle graze on young sorghum shoots, which naturally contain cyanogenic compounds capable of releasing cyanide. Once absorbed, cyanide disrupts cellular respiration by preventing cells from utilizing oxygen, resulting in rapid tissue damage and cell death. The condition is particularly common in ruminants and is characterized by its acute onset and high fatality rate. In many cases, affected animals are found dead without prior warning, although signs such as difficulty breathing, muscle tremors, and bright red or congested mucous membranes may be observed before death. Due to its rapid action and severe consequences, cyanide poisoning remains an important health and management challenge in cattle production.
2026-06-30 | Case Report: Successful multimodal management of a lethal cyanide poisoning - insights into the role of early blood purification and potential bedside monitoring indicators.
This article reports a rare and lethal case of cyanide poisoning, aiming to explore its early diagnosis and successful treatment strategies. Upon admission, the patient presented with cardiac and respiratory arrest, deep coma, and severe metabolic acidosis. The core resuscitation measures included early mechanical ventilation, vasoactive drug support, bicarbonate therapy, and the early initiation of continuous blood purification as part of a multimodal strategy. We observed that a combination of elevated central venous partial pressure of carbon dioxide (PvCO2) and elevated lactate provided potential bedside clues for early suspicion of cyanide poisoning. During treatment, a rise in PvCO2 accompanied by a decrease in lactate was noted, which may serve as a hypothesis-generating observation for treatment response, acknowledging the influence of multiple concurrent interventions. The patient recovered substantially after comprehensive treatment. This case provides valuable experience for the treatment of cyanide poisoning.
2026-06-07 | Cobalamin (Vitamin B12) in Clinical Practice: Indications, Molecular Mechanisms, and Management of Deficiency
Cobalamin (vitamin B12) is an essential micronutrient and a potent pharmacological agent with well-established roles in DNA synthesis, myelin maintenance, and cellular metabolism. This scholarly review provides a comprehensive, clinically oriented analysis of cobalamin’s indications, mechanisms of action, pharmacokinetics, adverse effect profiles, contraindications, and monitoring parameters. The discussion distinguishes between FDA-approved indications—including pernicious anemia, atrophic gastritis, chronic acid suppression, metformin use, gastrectomy, small bowel bacterial overgrowth, Diphyllobothrium latum infection, pancreatic insufficiency, and dietary deficiency—and off-label uses such as cyanide poisoning and vasoplegia. Emphasis is placed on the dual cofactor functions of cobalamin in the methionine synthase and methylmalonyl-CoA mutase pathways, explaining the pathophysiological consequences of deficiency, including megaloblastic anemia and subacute combined degeneration of the spinal cord. The review critically compares oral versus parenteral administration, highlighting the clinical utility of high-dose oral cobalamin even in intrinsic factor deficiency. Monitoring strategies, including reticulocyte response, normalization of methylmalonic acid and homocysteine, and vigilance for hypokalemia or thrombocytosis, are outlined. Importantly, this review underscores the necessity of an interprofessional team approach—integrating clinicians, pharmacists, nurses, dietitians, and specialists—to achieve optimal patient outcomes. No significant toxicity is associated with cobalamin, but hypersensitivity, Leber optic nerve atrophy, and drug interactions require careful consideration. Ultimately, this activity aims to equip healthcare professionals with the conceptual and practical tools to diagnose, treat, and manage cobalamin deficiency effectively across diverse clinical contexts.
2026-06-02 | A pilot study in the swine model of lethal cyanide intoxication indicates efficacy of a platinum-methionine complex countermeasure.
Cyanide presents a chemical security threat because of its wide availability, due to industrial uses, and significant toxicity. Platinum-thioether complexes are a recent addition to candidate antidotes, showing efficacy in mouse models of hydrogen cyanide inhalation and reversing toxicity measures in rabbits. This pilot study evaluated the effectiveness of a platinum-methionine complex (Met2Pt), a potent lead candidate, in a lethal swine model, which provides a solid foundation for future research. Potassium cyanide (0.2 mg/kg/min; IV) was infused into anesthetized swine until 6 min post-apnea. Met2Pt (2.9 mg Pt/kg in 3 mL) or 100 mM phosphate buffer vehicle (3 mL) were then administered intravenously (IV) or intramuscularly (IM). Vital signs, metabolites, and pharmacokinetics were monitored for > 90 min. IV Met2Pt was highly efficacious compared to all other treatments, rescuing all swine in the group and reversing cyanide-derangements in lactate concentration (Welch One-Way ANOVA, p < 10- 4), blood oxygenation (p = 0.002), etc. IM Met2Pt did not significantly improve survival due to lower systemic availability (7%). The results of this pilot study indicate that Met2Pt is efficacious via the IV route, while IM availability of Met2Pt is a limiting factor.
proteins
2026-08-19 | Evaluation of PEGylated Methemoglobin for Sequestration of Cyanide, Azide, and Sulfide in In Vitro Binding Models.
Cyanide, azide, and sulfide are potent inhibitors of mitochondrial enzymes that disrupt cellular energy metabolism and can cause rapid, potentially fatal outcomes. Effective treatments for these toxic anions remain limited, underscoring the need for broadly acting antidotal strategies. Methemoglobin (methHb), the ferric form of hemoglobin (hHb), binds these ligands with high affinity and acts as a mechanistic scavenger by sequestering toxic anions before they can interact with mitochondrial targets. PEGylation of methHb (met-PEG-hHb) offers a strategy to improve methHb molecular stability and may reduce potential oxidative side effects while altering protein interactions that could influence future in vivo pharmacokinetic behavior. In this study, we characterize various met-PEG-hHbs as multiligand scavengers using in vitro binding models. Size-exclusion high-performance liquid chromatography (SEC-HPLC) and dynamic light scattering (DLS) confirm that PEGylation preserves molecular size and homogeneity after oxidation, while circular dichroism spectroscopy demonstrates maintenance of protein secondary structure. UV-vis spectroscopy and stopped-flow kinetics reveal that met-PEG-hHb rapidly and efficiently binds cyanide, azide, and sulfide. These findings show that PEGylation stabilizes methHb while preserving its ability to bind cyanide, azide, and sulfide in vitro, supporting met-PEG-hHb as a promising platform for further preclinical evaluation as a broad-spectrum toxic anion scavenger.
2026-02-24 | Evaluation of methemoglobin and polymerized methemoglobin for detoxification of cyanide, azide, and sulfide in in vitro binding models.
Cyanide, azide, and sulfide are fast-acting cellular poisons that inhibit mitochondrial respiration by targeting metal centers within key enzymes, leading to rapid energy failure and potentially lethal metabolic collapse. Despite their clinical relevance, specific antidotes capable of broadly neutralizing these toxic anions remain limited. Methemoglobin (methHb), the ferric form of hemoglobin with high affinity for these ligands, has been recognized as a mechanistic antidote capable of sequestering toxic anions before they reach mitochondrial targets. Polymerized hemoglobin (PolyhHb) and its oxidized counterpart, polymerized methemoglobin (metPolyhHb), offer a promising strategy to potentially enhance the stability, circulation time, and safety profile of methHb-based detoxification systems. In this study, we characterize methHb and metPolyhHb as multi-ligand scavengers using in vitro binding models. High-performance liquid chromatography (HPLC) and dynamic light scattering (DLS) demonstrated that oxidation of PolyhHb does not alter its molecular size or distribution. Circular dichroism confirmed preservation of secondary structure following oxidation. Using UV-visible spectroscopy and stopped-flow kinetics, we show that both methHb and metPolyhHb rapidly and efficiently bind cyanide, azide, and sulfide. These findings demonstrate that PolyhHb retains structural integrity upon oxidation and maintains strong detoxification capability across multiple toxic anions, supporting its potential as a versatile platform for broad-spectrum antidotal development.
2025-12-10 | NirA is a Cyanide-Tolerant Nitrite Reductase Which Protects Pseudomonas aeruginosa From Self-Poisoning.
Host production of nitric oxide in response to P. aeruginosa results in accumulation of nitrite and nitrate at the infection site, with both utilised for anaerobic respiration to support survival. Nitric oxide and nitrite also act as aerobic respiratory inhibitors. P. aeruginosa must overcome these toxic metabolites alongside self-produced cyanide to persist at the infection site. We previously identified a novel nitrite reductase (NirA) that supports P. aeruginosa virulence in a wide range of infection models. In this work, we demonstrate that mutation of nirA inhibits growth of P. aeruginosa at reduced oxygen tensions in the presence of nitrite or nitrate, with this phenotype shown to be dependent on cyanide. NirA is a siroheme-dependent enzyme, a classical target for inhibition with cyanide. Biochemical characterisation confirms that NirA is a novel cyanide-tolerant nitrite reductase, which supports reduction of nitrite in the presence of cyanide. We hypothesise that NirA enables detoxification of nitrite to prevent build-up of multiple respiratory inhibitors and facilitate cyanide-resistant aerobic respiration at low oxygen tensions. Through targeting effectors of these resistance mechanisms, we could promote P. aeruginosa self-poisoning and prevent adaptation to the reduced oxygen environment typically encountered by P. aeruginosa in biofilms and during infection.
2024-08-13 | Characterization of rhodanese synthesized by the wild and EMS-mutated Klebsiella oxytoca JCM1665
Cyanide poisoning remains a significant concern for both civilian and military personnel worldwide. Rhodanese, a cyanide detoxify enzyme produced by the wild (KOJCM1665) and two selected mutant strains (KOJCM1665c and KOJCM1665d) of Klebsiella oxytoca JCM 1665 was purified and characterized using a combination of standard techniques. Extracellular rhodanese yield of the wild and selected mutants were 6.2 ± 0.6, 26.7 ± 0.7 and 18.3 ± 0.3 U/mL respectively. The overall levels of recovery of rhodanese activity and fold after purification were 49 %, 66 %, and 58 % and 2.6, 2.6, and 2.3 % for the wild, KOJCM 1665c, and KOJCM 1665d, respectively. The native molecular weights of the three enzyme preparations were 35.1, 34.9, and 34.8 kDa, while the subunit molecular weight was 35 kDa for all the enzymes. The optimum activity of the enzymes was observed at 50 °C and pH 6.0. The real km of the three enzyme preparations for KCN as a substrate were 1.03 × 10−3, 0.95 × 10−3, and 0.80 × 10−3 M, respectively, while the km for the second substrate (Na2S2O3) were 0.59 × 10−3, 0.49 × 10−3, and 0.69 × 10−3 M, respectively. The substrate specificity study showed that the enzyme preferred sodium thiosulfate as the substrate. Metal ions such as Na+ and K+ had significantly greater inhibitory effects on enzyme activity. This study demonstrated the potential of enhancing K. oxytoca JCM 1665 to overexpress extracellular rhodanese, and the physicochemical properties of the enzyme hold significant promise as a target for improving the efficiency of cyanide bioremediation processes.
2023-12-16 | Elucidating the binding properties of methemoglobin in red blood cell to cyanide, hydrosulfide, and azide ions using artificial red blood cell.
Methemoglobin (metHb), the oxidized form of hemoglobin, lacks the ability of reversible oxygen binding; however, it has a high binding affinity to toxic substances such as cyanide, hydrosulfide, and azide. This innate property of metHb offers the clinical option to treat patients poisoned with these toxins, by oxidizing the endogenous hemoglobin in the red blood cells (RBCs). The binding properties of naked metHb (isolated from RBC) with these toxins has been studied; however, the binding behaviors of metHb under the intracellular conditions of RBC are unclear because of the difficulty in detecting metHb status changes in RBC. This study aimed to elucidate the binding properties of metHb in RBC under physiological and poisoned conditions using artificial RBC, which was hemoglobin encapsulated in a liposome. The mimic-circumstances of metHb in RBC (metHb-V) was prepared by oxidizing the hemoglobin in artificial RBC. Spectroscopic analysis indicated that the metHb in metHb-V exhibited a binding behavior different from that of naked metHb, depending on the toxic substance: When the pH decreased, (i) the cyanide binding affinity of metHb-V remained unchanged, but that of naked metHb decreased (ii) the hydrosulfide binding affinity was increased in metHb-V but was decreased in naked metHb. (iii) Azide binding was increased in metHb-V, which was similar to that in naked metHb, irrespective of the pH change. Thus, the binding behavior of intracellular metHb in the RBC with cyanide, hydrosulfide, and azide under physiological and pathological conditions were partly elucidated using the oxidized artificial RBC.
cell therapies
2025-07-25 | Potential of some lactic acid bacteria inoculants in the bioremediation of cyanogenic glycosides in sorghum straw silage
Sorghum is a vital economic crop in China, generating substantial amounts of crop residues annually, which necessitates research into its comprehensive utilization. Cyanogenic glycosides, a class of metabolites widely distributed in sorghum and other plant species, tend to release hydrogen cyanide under enzymatic action, posing a potential poisoning risk to animals. In the present study, to enhance the fermentation quality of sorghum straw silage, β-glucosidase-producing lactic acid bacteria isolated from fresh sorghum straw were employed as inoculants. A systematic investigation was conducted on the microbial community structure and metabolomic profiles following 60 days of fermentation, utilizing untargeted metabolomics analysis to elucidate the mechanisms by which β-glucosidase-producing lactic acid bacteria influence sorghum straw silage fermentation quality, as well as the degradation of dhurrin and reduction of hydrocyanic acid levels in sorghum. The results demonstrated that the silage fermentation quality in the lactic acid bacteria-supplemented experimental group was significantly improved compared to the control group. Attributed to the modulation of metabolic pathways, the levels of dhurrin and hydrocyanic acid exhibited a significant decrease with extended ensiling duration. At the metabolite level, biological pathways involved in steroid biosynthesis, terpenoid synthesis, and carotenoid synthesis were upregulated during different stages of ensiling. These metabolites not only enhance the nutritional value of the feed, but also possess anti-inflammatory and health-promoting properties, thereby further underscoring the positive regulatory role of lactic acid bacteria in the silage process.
2024-10-09 | Detoxification of hydrocyanide by fermentation of apricot seeds with probiotic Lactobacillus strains isolated from breast milk
Many plants produce substances known as cyanogenic glycosides, which, when hydrolyzed, can release hydrogen cyanide. These include apricot (Prunus armeniaca L.) seeds, the subject of the study presented here. Amygdalin when metabolized, turns into hydrocyanide, which can cause cyanide poisoning if ingested in large quantities. The current study used Lactobacillus spp. that were isolated from breast milk. High concentrations of hydrocyanic acid, which apricot seeds contain, are dangerous during fermentation by Lactobacillus spp. The aim of the present study is to recognize the most effective methods for detoxifying apricot seeds and fermented amygdalin extract, while conserving or enhancing the physical properties, chemical structure, minerals and amino acids. Activation of bacterial isolates was followed by fermentation. Next a cellular cytotoxicity test for extract was conducted. After fermentation, we evaluated the cytotoxic effect on cancer and normal cell in vitro. After fermentation, a detoxification of apricot seeds was shown resulting from the presence of compound and improvement of vitamins formed due to fermentation. The use of Lactobacillus bacteria isolated from breast milk resulted in the production of a new fermented milk product containing aqueous extract of apricot seeds free from life-threatening toxicity. Fermentation produced a new probiotic with less toxic hydrocyanide, fatty acid, and amino acid, showing cytotoxic effects on cancer cells and minimal toxicity to normal cells.
2023-08-16 | The isolation of rumen enterococci strains along with high potential utilizing cyanide.
Cyanogenic glycosides in forage species and the possibility of cyanide (CN) poisoning can have undesirable effects on ruminants. The literature estimates that unknown rumen bacteria with rhodanese activity are key factors in the animal detoxification of cyanogenic glycosides, as they are capable of transforming CN into the less toxic thiocyanate. Therefore, identifying these bacteria will enhance our understanding of how to improve animal health with this natural CN detoxification process. In this study, a rhodanese activity screening assay revealed 6 of 44 candidate rumen bacterial strains isolated from domestic buffalo, dairy cattle, and beef cattle, each with a different colony morphology. These strains were identified as belonging to the species Enterococcus faecium and E. gallinarum by 16S ribosomal DNA sequence analysis. A CN-thiocyanate transformation assay showed that the thiocyanate formation capacity of the strains after a 12 h incubation ranged from 4.42 to 25.49 mg hydrogen CN equivalent/L. In addition, thiocyanate degradation resulted in the production of ammonia nitrogen and acetic acid in different strains. This study showed that certain strains of enterococci substantially contribute to CN metabolism in ruminants. Our results may serve as a starting point for research aimed at improving ruminant production systems in relation to CN metabolism.
2023-03-17 | CRISPR-Cas9-mediated knockout of CYP79D1 and CYP79D2 in cassava attenuates toxic cyanogen production
Cassava (Manihot esculenta) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces the neurotoxin cyanide and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. This problem is further exacerbated by drought conditions which increase this toxin in the plant. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444; the West African, farmer-preferred cultivar TME 419; and the improved variety TMS 91/02324. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. The congruence of results across accessions indicates that our approach could readily be extended to other preferred or improved cultivars. This work demonstrates cassava genome editing for enhanced food safety and reduced processing burden, against the backdrop of a changing climate.
2022-09-28 | Whole-genome analysis guided molecular mechanism of cyanogenic glucoside degradation by yeast isolated from Prunus mume fruit syrup.
Consumption of fermented Prunus mume fruit (maesil) sugar syrup raise a health concern due to the presence of the cyanogenic glucoside amygdalin. The goal of the present study was to investigate the amygdalin degradation potential and genome profile of the native microbes found in maesil syrup. The microbial profile analysis revealed that yeast is the predominant microorganism native to maesil syrup and that the isolated yeast cells showed a remarkable potential for amygdalin reduction (99.7%). Moreover, the reduction in amygdalin was inversely proportional to the growth of the isolated yeast. The whole-genome analysis revealed that the isolated yeast is Zygosaccharomyces rouxii (genome size 10 Mb, 39.25% of GC content). Of the 5250 genes (64.88%) predicted in the Z. rouxii genome, 5245 (99.90%) were annotated using NCBI Non-Redundant, UniProt, and InterProScan databases. The genome of the isolated Z. ruoxii harbored 2.03% of repeats and 0.68% of non-coding RNAs. Protein prediction indicated that β-glycosidases and hydroxynitrile lyase may play a key role in amygdalin degradation. The predicted degradation initiated by β-glycosidases that hydrolyze α-glucosidic bonds of amygdalin results in α-hydroxy nitriles (cyanohydrins) that are subsequently converted into carbonyl compounds (benzaldehyde) and hydrogen cyanide catalyzed by hydroxynitrile lyases. Present findings provide valuable data for constructing engineered microorganisms that can degrade amygdalin. Further analysis of Z. rouxii may elucidate the exact mechanism of amygdalin reduction in the production of maesil syrup.
gene therapies
2025-12-12 | Sorghum Poisoning in Livestock: Mechanisms, Risks, and Sustainable Mitigation Strategies
Sorghum (Sorghum bicolor L. Moench) is a vital drought-tolerant crop cultivated in arid and semi-arid regions, serving as both food and fodder. However, under environmental stress, sorghum accumulates cyanogenic glucosides (primarily dhurrin), which hydrolyze into toxic hydrogen cyanide (HCN) upon ingestion, posing lethal risks to livestock. This review examines the biochemical pathways of dhurrin synthesis and HCN release, highlighting key risk factors including drought, frost, and improper grazing management. This study is structured to first elucidate the biochemical and risk factors behind sorghum poisoning, then to evaluate a suite of integrated mitigation strategies—from agroforestry to genetic solutions—and finally to discuss the implementation pathways through education and policy.We evaluate mitigation strategies such as agroforestry integration—using nitrogen-fixing trees (Leucaena leucocephala, Gliricidia sepium) to reduce plant stress and provide alternative fodder—alongside feed management techniques (ensiling, sulfur supplementation). Additionally, we explore genetic solutions (low-dhurrin cultivars developed via CRISPR-Cas9) and microbial/phytoremediation approaches (Pseudomonas fluorescens, Eucalyptus camaldulensis) for cyanide detoxification. Farmer education on risk recognition and safe practices emerges as a critical preventive measure. By synthesizing current research, this paper proposes integrated, sustainable strategies to minimize sorghum poisoning while maintaining agricultural productivity in vulnerable regions.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
12 orphan drug designations for Cyanide poisoning, including 2 approved therapies.
12 orphan drug designations for Cyanide poisoning, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
hydroxocobalamin | small molecules | FDA | — | Amneal EU, Limited |
sodium nitrite and sodium thiosulfate [Nithiodote] | small molecules | FDA | Approved | Hope Pharmaceuticals |
sodium nitrite | small molecules | FDA | — | Hope Pharmaceuticals |
Sodium nitrite/sodium thiosulfate | small molecules | FDA | — | Keystone Pharmaceuticals, Inc. |
Amyl nitrite, sodium nitrite, sodium thiosulfate | small molecules | FDA | — | Akorn, Inc. |
Sodium thiosulfate and sodium nitrite | small molecules | FDA | — | Akorn, Inc. |
Sodium thiosulfate, sodium nitrite, amyl nitrite | small molecules | FDA | — | Keystone Pharmaceuticals, Inc. |
Sodium dichloroacetate [Sodium dichloroacetate for injection] | small molecules | EMA | — | EBD Group GmbH |
Hydroxocobalamin [Cyanokit] | small molecules | FDA | Approved | SERB, S.A. |
ALPHA-1-ACID GLYCOPROTEIN | proteins | EMA | — | Bio Products Laboratory Limited |
Hydroxocobalamin | small molecules | FDA | — | Rare Disease Therapeutics, Inc. |
Hydroxycobalamin/sodium thiosulfate | small molecules | FDA | — | Hall, Alan H., M.D. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.