RARE DISEASE
Colchicine poisoning
Colchicine poisoning
Colchicine poisoning
Drug discovery
1
drug
With orphan designation
Overview
Colchicine poisoning, characterized by a narrow therapeutic index, causes delayed-onset gastrointestinal symptoms (nausea, vomiting, diarrhea) progressing to multiorgan failure (cardiotoxicity, bone marrow suppression, hepatic/renal injury) within 24–72 hours [1][6][12]. Mortality rates exceed 10%, particularly with doses >0.5 mg/kg [2][4][14]. Management prioritizes early gastrointestinal decontamination (activated charcoal) and aggressive supportive care, including fluid resuscitation, vasopressors, and granulocyte colony-stimulating factor (G-CSF) for myelosuppression [3][6][16]. No specific antidote exists [12].
Burden
Mortality: 10–14.3% in acute overdose, rising with delayed presentation or comorbidities [2][4][12].
Resource utilization: High ICU admission rates (42.8%) and prolonged hospitalization [4][14].
Complications: Long-term organ dysfunction (neuropathy, cardiomyopathy) and rebound leukocytosis during recovery [8][16].
Therapies
Decontamination: Activated charcoal within 1–2 hours of ingestion [1][6].
Supportive care: Fluid/electrolyte replacement, vasopressors for shock, G-CSF for neutropenia, and mechanical ventilation for respiratory failure [3][6][16].
Experimental therapies: Plasmapheresis and continuous renal replacement therapy (CKRT) in severe cases [3][18].
Categories: rare disorders due to toxic effects
Research Papers
208 drug discovery papers about Colchicine poisoning, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
208 drug discovery papers about Colchicine poisoning, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-04-03 | Successful Management of Accidental Colchicine Intoxication After Ingestion of Colchicum autumnale: A Case Report
We report the case of a 58-year-old man who experienced moderate renal and liver impairment after accidental poisoning with Colchicum autumnale, which he confused with wild garlic (Allium ursinum). Colchicum autumnale contains colchicine, a toxic compound that disrupts cell division. The patient received intensive care therapy, intravenous lipid emulsion, vitamin K supplementation, and N-acetylcysteine replacement. After seven days of hospitalisation, he was discharged in good health. This case highlights the importance of patients presenting at the emergency department with uncertain anamnesis, gastrointestinal symptoms or recent consumption of perennial plants before symptom onset, which should raise the suspicion of intoxication. Early diagnosis, organ-specific supportive therapy, and timely initiation of disease-specific therapy are crucial for improving patients’ outcomes.
2026-02-23 | Adsorption of colchicine, hydroxychloroquine, ibuprofen, and strychnine to activated charcoal.
Activated charcoal is commonly used in the management of xenobiotics to reduce systemic absorption, but data supporting its efficacy for certain xenobiotics remain limited. Quantitative data describing adsorption of colchicine, hydroxychloroquine, ibuprofen, and strychnine help inform emergency treatment options for the management of a xenobiotic ingestion. To evaluate the adsorption of colchicine, hydroxychloroquine, ibuprofen, and strychnine to activated charcoal by quantifying adsorption kinetics and fitting isotherm data to characterize binding behavior and xenobiotic-specific effective doses. Kinetics and adsorption isotherm experiments were performed in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The Langmuir isotherm model was used to estimate maximum adsorption capacity and binding affinity. The Freundlich isotherm model was used to derive relative adsorption capacity and adsorption favorability. Optimal charcoal-to-xenobiotic ratios for ≥95% adsorption were determined for each xenobiotic in both media. Xenobiotics adsorbed efficiently to activated charcoal, with higher adsorption generally observed in simulated intestinal fluid. Freundlich modeling provided better fits across xenobiotics. Colchicine adsorbed efficiently, with an 8:1 ratio of activated charcoal-to-xenobiotic required to achieve ≥95% xenobiotic adsorption across both media. Hydroxychloroquine required a higher ratio to achieve ≥95% adsorption in simulated gastric fluid (10:1) versus simulated intestinal fluid (7:1). Strychnine also required a higher activated charcoal-to-xenobiotic ratio in simulated gastric fluid (11:1) than simulated intestinal fluid (8:1) to achieve ≥95% adsorption. Ibuprofen required an 11:1 ratio to achieve ≥95% adsorption in simulated intestinal fluid. A standard 50 g dose of activated charcoal may effectively adsorb toxic doses of colchicine and strychnine. However, large overdoses of hydroxychloroquine and ibuprofen may need additional doses of activated charcoal. This study supports the targeted use of activated charcoal in colchicine, hydroxychloroquine, ibuprofen, and strychnine ingestions. Isotherm modeling reveals xenobiotic-specific differences in adsorption efficiency that may inform clinical decisions regarding dose, timing, and the potential use of additional charcoal administration.
2025-02-19 | Pumpkin seeds oil rescues colchicine-induced neurotoxicity in rats via modifying oxidative stress, DNA damage, and immunoexpression of BDNF and GFAP.
Colchicine (CHC), a poisonous plant alkaloid, has been widely utilized for decades in the treatment of gout, but has a rather low therapeutic index, which causes oxidative stress leading to cognitive impairment, brain damage, apoptosis, and hitopathological alterations in humans and experimental animals. The present investigation evaluated the potential palliative effect of the pumpkin seeds oil (PSO) at a dose of 4 ml/kg b.wt against CHC (0.6 mg/kg b.wt) -induced neurotoxic and neurobehavioral effects in rats. Forty male rats weighing 245-260 g were assigned to four groups. The results displayed that CHC exposure induced neurobehavioral disorders and a remarkable decline in the serotonin and dopamine levels and the immunoexpression of BDNF and GFAP in the brain. Besides, CHC treatment evoked brain oxidative stress, as manifested by depleted antioxidant enzyme activities and elevated malondialdehyde (MDA) and protein carbonyl (PC) levels. Also, CHC triggered brain DNA damage, as indicated by a marked increment in the brain 8-Hydroxyguanosine (8-OHdG) level. However, concurrent treatment with the PSO effectively attenuated the CHC-induced toxic effects as evidenced by a noticeable increase in the serotonin (33 ± 3.05) and dopamine (2.48 ± 0.40) concentrations, and the BDNF and GFAP immunoexpression in the brain. Moreover, PSO mitigated CHC-induced brain oxidative stress and DNA damage as shown by elevated antioxidant enzyme activities (164 ± 3.46 SOD and 7.55 ± 0.43 CAT) and reduced MDA (1.62 ± 0.23), PC (1.35 ± 0.23), and 8-OHdG (3.02 ± 0.33) levels. These results concluded that PSO could serve as a therapeutic strategy to ameliorate the neurotoxic and neurobehavioral impacts of CHC.
2025-01-27 | WCN25-3435 SUCCESSFUL MANAGEMENT OF COLCHICINE TOXICITY-INDUCED MULTI-ORGAN FAILURE THROUGH CONTINUOUS RENAL REPLACEMENT THERAPY
Colchicine, is a well-known treatment for gout and pericarditis, but its narrow therapeutic window poses a significant risk for toxicity, even at therapeutic doses. We present the case of a woman who suffered a severe colchicine poisoning resulting in multi-organ failure, including acute kidney injury (AKI), and her complete recovery following renal replacement therapy.
2024-11-21 | Comprehensive multi-omics analysis elucidates colchicine-induced toxicity mechanisms and unveils the therapeutic potential of MLN4924 and kinase inhibitors.
Colchicine is a widely prescribed anti-inflammatory drug for the treatment of gout, familial Mediterranean fever and pericarditis, but its narrow therapeutic window presents a significant risk of severe toxicity. Despite its clinical relevance, the molecular mechanisms underlying colchicine's pharmacological effects and associated toxicity and explored potential therapeutic interventions to mitigate its adverse effects. We showed the colchicine's impact on cellular morphology in human umbilical vein endothelial cells (HUVEC) and HeLa cells including cell rounding and detachment following 24 h of exposure that revealed pronounced cytotoxic effects. We then established a large-scale screening model to identify small molecules capable of reversing colchicine-induced cellular toxicity, and identified MLN4924, an inhibitor of the Cullin-RING E3 ligase (CRL) system, as a promising candidate for mitigating colchicine-induced cellular injury. Through a comprehensive multi-omics approach including transcriptomics, proteomics, phosphoproteomics and ubiquitinomics, we systematically characterized the molecular perturbations caused by colchicine and delineated the protective mechanisms of MLN4924. We found that MLN4924 exerted its protective effects by modulating critical cellular pathways, specifically preventing the dysregulation of cell cycle progression, mitotic disruption and microtubule destabilization triggered by colchicine. Furthermore, proteomic and phosphoproteomic analyses revealed significant alterations in kinase signaling networks, with combined inhibition of CDK1 and PAK1 emerging as an effective strategy to counteract colchicine-induced cellular dysfunction. These results not only provide a detailed molecular characterization of colchicine toxicity but also identify key therapeutic targets, laying the groundwork for the development of targeted interventions to mitigate colchicine-induced adverse effects in clinical practice.
proteins
2025-10-29 | Successful multimodal intensive care management including early plasmapheresis and granulocyte colony stimulating factor in severe colchicine poisoning: A case report.
Colchicine is a narrow therapeutic index drug widely used in the treatment of inflammatory diseases such as acute gout attacks and Familial Mediterranean Fever (FMF). In case of overdose, the risk of toxicity is high and can rapidly lead to multiple organ failure. The lack of an antidote for colchicine toxicity continues the search for a definitive treatment. We present a case of severe colchicine toxicity managed successfully with early initiation of therapeutic plasma exchange (TPE), intensive supportive care including noninvasive ventilation, hemodynamic stabilization, electrolyte management, and granulocyte colony- stimulating factor (G-CSF) therapy. This multimodal intensive care approach resulted in complete recovery.
2023-08-16 | Drastic alterations in the loop structure around colchicine upon complex formation with an engineered lipocalin indicate a conformational selection mechanism
Using Anticalin technology, a lipocalin protein dubbed Colchicalin, with the ability to bind the toxic plant alkaloid colchicine with picomolar affinity, has previously been engineered, thus offering a potential antidote in vivo and also allowing its sensitive detection in biological samples. To further analyze the mode of ligand recognition, the crystal structure of Colchicalin is now reported in its unliganded form and is compared with the colchicine complex. A superposition of the protein structures revealed major rearrangements in the four structurally variable loops of the engineered lipocalin. Notably, the binding pocket in the unbound protein is largely occupied by the inward-bent loop #3, in particular Ile97, as well as by the phenylalanine side chain at position 71 in loop #2. Upon binding of colchicine, a dramatic shift of loop #3 by up to 11.1 Å occurs, in combination with a side-chain flip of Phe71, thus liberating the necessary space within the ligand pocket. Interestingly, the proline residue at the neighboring position 72, which arose during the combinatorial engineering of Colchicalin, remained in a cis configuration in both structures. These findings provide a striking example of a conformational adaptation mechanism, which is a long-known phenomenon for antibodies in immunochemistry, during the recognition of a small ligand by an engineered lipocalin, thus illustrating the general similarity between the mode of antigen/ligand binding by immunoglobulins and lipocalins.
2023-06-01 | In vivo neutralization of colchicine toxicity by a PASylated anticalin in a rat model.
We have investigated the pharmacokinetics (PK) and in vivo activity of an Anticalin exhibiting picomolar affinity towards colchicine, a plant toxin with low tolerable dose in humans. PK analysis of the 20-kDa "Colchicalin" protein in male Sprague Dawley rats (n = 3) revealed a very short plasma half-life (3.5 min), which was prolonged 21-fold via genetic fusion with a 200-residue Pro/Ala sequence (PASylation). The scavenging activity of the PASylated Colchicalin was investigated over 3.5 h via stoichiometric application following a sub-toxic i.v. dose of colchicine on anesthetized rats (n = 2) leading to a rapid rise in total plasma colchicine concentration. We then established a 14-day intoxication model in rats (n = 3) at a 30 mg/kg p.o. colchicine dose which was characterized by severe weight loss, elevated neutrophil-to-lymphocyte ratio and shortened survival. PASylated Colchicalin administration at 4.2% of the neutralizing dose (125 mg/kg/day daily for 12 consecutive days) resulted in faster relief of the symptoms in 2/3 of animals (n = 6) compared to the control group without Colchicalin treatment (n = 5). Nevertheless, 1/3 of the rats died suddenly after the first Colchicalin injection, probably due to a steep rise in the total colchicine plasma concentration, which suggests further improvement of the dosing scheme prior to potential application in acute human colchicine poisoning.
2021-07-29 | Pathogenic characteristics and treatment in 43 cases of acute colchicine poisoning
Abstract Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5–0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries， include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration.
2021-05-12 | Poisoning with Soranjan (Colchicum): a case report
Introduction: Colchicine, which is derived from a herb called Colchicum is a medication used to treat gout. Colchicum itself can act as a deadly toxic herb in the case of over dose. This is a case report study which investigates a patient who was poisoned with Colchicum (Soranjan, what it is called in Iran). Description: The patient was a 44-year-old man who came to the emergency poisoning ward after a day of mountaineering and eating Soup. He had severe nausea and vomiting. The patient was admitted to the ICU two days later with a toxic general condition, complaining of chest pain, nausea, vomiting and shortness of breath. The patient lab tests showed elevated liver enzymes and pancytopenia. The patient respiratory distress developed and physician had to intubate the patient. The patient was treated with antibiotics, GCSF for pancytopenia and antioxidant to protect the liver. Conclusion: The patient responded to broad spectrum antibiotic, antifungal and GCSF. paying attention to the patient’s history was the key of success to diagnosis.
cell therapies
2026-05-06 | A large pediatric cohort of colchicine intoxication: prognostic factors and experience with rapid sequence apheresis.
Severe colchicine intoxication often leads to multi-organ failure and death. With no specific antidote and ineffective conventional elimination methods, we hypothesized that rapid sequence apheresis could reduce the intravascular colchicine reservoir. This study describes pediatric colchicine poisoning, focusing on dose-related outcomes and the clinical role of rapid sequence apheresis. This retrospective observational analysis included children admitted to a tertiary pediatric intensive care unit for colchicine poisoning (2011-2025). Clinical data, ingested dose, organ involvement, and patient characteristics were evaluated. Logistic regression and ROC analyses were used to identify variables associated with disease severity and poor outcomes, including those treated with rapid sequence apheresis. Eighty-four patients were included (median dose: 0.3 mg/kg). Across dose groups (<0.5, 0.5-0.8, and >0.8 mg/kg), higher doses correlated with increased frequency of diarrhea (20.6%, 57.1%, and 57.1%, respectively, P = 0.071) and cardiovascular involvement (20.6%, 50%, and 71.4%, respectively; P = 0.004). Logistic regression showed that diarrhea significantly increased the likelihood of cardiovascular complications (OR: 3.24, P = 0.006). The ROC analysis identified thresholds of >0.39 mg/kg and >24 mg total dose as predictors of cardiovascular toxicity. Seventeen patients (20.2%) underwent rapid sequence apheresis. Despite advanced supportive care, five patients died, including two who ingested <0.5 mg/kg and received rapid sequence apheresis. Our findings suggest that higher ingested doses and early gastrointestinal manifestations such as diarrhea may serve as indicators of increased risk for cardiovascular complications in pediatric colchicine intoxication. In addition, clinically significant toxicity may occur at doses lower than traditionally reported thresholds. Pediatric colchicine intoxication may lead to significant cardiovascular complications even at relatively lower doses. Early recognition of high-risk clinical indicators, including gastrointestinal symptoms, leukocytosis, and ingested dose, may facilitate clinical risk stratification and early identification of patients at increased risk of adverse outcomes. Rapid sequence apheresis was used in selected severe cases in our cohort; however, its therapeutic role requires further investigation.
2022-10-03 | Colchicine Poisoning Cases in a Pediatric Intensive Care Unit: A Twenty-Year Study.
Colchicine intoxication is rare but potentially fatal. The toxic dose of colchicine is not well established; it has been reported that major toxicity starts after doses of 0.5 mg/kg. We aimed to evaluate the demographic, clinical aspects, treatments, and outcome of colchicine toxicity cases in the pediatric intensive care unit (PICU). We collected the data of patients aged between 0 and 18 years, admitted to Ankara University Faculty of Medicine PICU for colchicine poisoning (n = 22), from October 1999 to January 2020, retrospectively. Data extracted from the cases included age, sex, chronic condition, time between intake of drug and admission to PICU, source of drug, amount of drug ingested, other drug intake, symptoms, clinical findings, cardiac involvement, laboratory results, time of stay in PICU, treatment, and outcome. Patients' age ranged from 7 months to 17 years. Median age was 86 months. The most common symptom at time of admission was vomiting, occurring in 13 (59%) of the patients. Two of the patients presented with change in mental status. Time between taking medication and applying to the hospital ranged from half an hour to 4 days. Medication intake of 3 of 22 patients was more than 0.5 mg/kg. One patient whose parents' best estimate of dose ingested was 0.48 mg/kg died because of the development of multiorgan failure. One patient who ingested 0.4 mg/kg of colchicine underwent plasma exchange and recovered without any complications. Colchicine poisoning has a high risk of mortality, and death can be seen in doses less than a single acute dose of 0.5 mg/kg. These patients need close monitoring because there is always a risk of them to require aggressive support. Prognosis is poor in patients who have rapidly developing hemodynamic failure.
2019-01-01 | Plasmapheresis in Acute Intoxication and Poisoning
The chapter will: Present an overview of the possible mechanisms of action of plasmapheresis in poisoning and drug overdose. Review the pharmacokinetic factors that affect the elimination of poisons/drugs by plasmapheresis. Highlight the limitations of published studies on the efficacy of plasmapheresis in poisoning and drug overdose. Summarize published data on the efficacy of plasmapheresis for specific poisons and drugs.
2014-09-26 | Plasma Exchange Treatment in a Case of Colchicine Intoxication
Therapeutic Apheresis and DialysisVolume 19, Issue 1 p. 95-97 Letter to the Editor Plasma Exchange Treatment in a Case of Colchicine Intoxication Demet Demirkol, Demet Demirkol Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorBurcin N Karacabey, Burcin N Karacabey bnazlikaracabey@hotmail.com Department of Pediatrics, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorFatih Aygun, Fatih Aygun Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this author Demet Demirkol, Demet Demirkol Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorBurcin N Karacabey, Burcin N Karacabey bnazlikaracabey@hotmail.com Department of Pediatrics, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorFatih Aygun, Fatih Aygun Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this author First published: 26 September 2014 https://doi.org/10.1111/1744-9987.12226Citations: 14Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume19, Issue1February 2015Pages 95-97 RelatedInformation
2014-05-01 | ABSTRACT 795
Background and aims: Colchicine poisoning is an uncommon, but potentially life-threatening, toxicologic emergency. It has a narrow therapeutic index and even death can be occur in minor toxicity. Initial 36 to 72 hours after ingestion, death might be seen caused by hypovolemic shock, central nervous system damage, and cardiopulmonary insufficiency. All patients who had colchicine overdose should be followed and treated in the intensive care units and treatment is usually supportive. Aims: In this case, we presented a patient diagnosed as colchicine intoxication and treated with plasma exchange. Methods: A previously healthy 6-year-old girl was ingested lethal doses of colchicium and referred to our pediatric intensive care unit (PICU). During the admission she had acute respiratory distress syndrome (ARDS), elevated transaminase levels, diarrhea and coagulopathy. The two plasma exchange session were applied to the patient who had multiorgan insufficiency already. Results: Drug removal during plasmapheresis are sparse, -mostly case reports of overdoses have described the effects of plasmapheresis on pharmaceutical. In general, drugs with a low volume of distribution (Vd) and/or a high rate of protein binding are most likely to be removed during plasma exchange. Colchicine completely does not have these features. But in some cases, plasma exchange might be beneficial in the treatment of colchicine intoxications. Conclusions: As a result, we consider that plasma exchange can be beneficial in eradication of colchicine from the body as it tightly binds to the plasma proteins and also decrease the mortality caused by its intoxication.
antibodies
2022-08-19 | Ku70 affects the frequency of chromosome translocation in human lymphocytes after radiation and T-cell acute lymphoblastic leukemia
Abstract Background As one of the most common chromosomal causes, chromosome translocation leads to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of error-prone DNA repair and it may end in translocation. So far, the direct correlation between Ku70 and translocation has not been assessed. This study aimed to investigate the association between Ku70 and translocation in human lymphocytes after radiation and T-ALL. Methods Peripheral blood lymphocytes (PBLs) from volunteers and human lymphocyte cell line AHH-1 were irradiated with X-rays to form the chromosome translocations. Phytohemagglutinin (PHA) was used to stimulate lymphocytes. The frequency of translocation was detected by fluorescence in situ hybridization (FISH). Meanwhile, the expression of Ku70 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Furthermore, Ku70 interference, overexpression and chemical inhibition were used in AHH-1 cell lines to confirm the correlation. Finally, the expression of Ku70 in T-ALL samples with or without translocation was detected. Results The expression of Ku70 and frequencies of translocation were both significantly increased in PBLs after being irradiated by X-rays, and a positive correlation between the expression (both mRNA and protein level) of Ku70 and the frequency of translocation was detected (r = 0.4877, P = 0.004; r = 0.3038, P = 0.0358 respectively). Moreover, Ku70 interference decreased the frequency of translocations, while the frequency of translocations was not significantly affected after Ku70 overexpression. The expression of Ku70 and frequencies of translocation were both significantly increased in cells after irradiation, combined with chemical inhibition ( P < 0.01). The protein level and mRNA level of Ku70 in T-ALL with translocation were obviously higher than T-ALL with normal karyotype ( P = 0.009, P = 0.049 respectively). Conclusions Ku70 is closely associated with the frequency of chromosome translocation in human lymphocytes after radiation and T-ALL. Ku70 might be a radiation damage biomarker and a potential tumor therapy target.
small molecules
2026-04-03 | Successful Management of Accidental Colchicine Intoxication After Ingestion of Colchicum autumnale: A Case Report
We report the case of a 58-year-old man who experienced moderate renal and liver impairment after accidental poisoning with Colchicum autumnale, which he confused with wild garlic (Allium ursinum). Colchicum autumnale contains colchicine, a toxic compound that disrupts cell division. The patient received intensive care therapy, intravenous lipid emulsion, vitamin K supplementation, and N-acetylcysteine replacement. After seven days of hospitalisation, he was discharged in good health. This case highlights the importance of patients presenting at the emergency department with uncertain anamnesis, gastrointestinal symptoms or recent consumption of perennial plants before symptom onset, which should raise the suspicion of intoxication. Early diagnosis, organ-specific supportive therapy, and timely initiation of disease-specific therapy are crucial for improving patients’ outcomes.
2026-02-23 | Adsorption of colchicine, hydroxychloroquine, ibuprofen, and strychnine to activated charcoal.
Activated charcoal is commonly used in the management of xenobiotics to reduce systemic absorption, but data supporting its efficacy for certain xenobiotics remain limited. Quantitative data describing adsorption of colchicine, hydroxychloroquine, ibuprofen, and strychnine help inform emergency treatment options for the management of a xenobiotic ingestion. To evaluate the adsorption of colchicine, hydroxychloroquine, ibuprofen, and strychnine to activated charcoal by quantifying adsorption kinetics and fitting isotherm data to characterize binding behavior and xenobiotic-specific effective doses. Kinetics and adsorption isotherm experiments were performed in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The Langmuir isotherm model was used to estimate maximum adsorption capacity and binding affinity. The Freundlich isotherm model was used to derive relative adsorption capacity and adsorption favorability. Optimal charcoal-to-xenobiotic ratios for ≥95% adsorption were determined for each xenobiotic in both media. Xenobiotics adsorbed efficiently to activated charcoal, with higher adsorption generally observed in simulated intestinal fluid. Freundlich modeling provided better fits across xenobiotics. Colchicine adsorbed efficiently, with an 8:1 ratio of activated charcoal-to-xenobiotic required to achieve ≥95% xenobiotic adsorption across both media. Hydroxychloroquine required a higher ratio to achieve ≥95% adsorption in simulated gastric fluid (10:1) versus simulated intestinal fluid (7:1). Strychnine also required a higher activated charcoal-to-xenobiotic ratio in simulated gastric fluid (11:1) than simulated intestinal fluid (8:1) to achieve ≥95% adsorption. Ibuprofen required an 11:1 ratio to achieve ≥95% adsorption in simulated intestinal fluid. A standard 50 g dose of activated charcoal may effectively adsorb toxic doses of colchicine and strychnine. However, large overdoses of hydroxychloroquine and ibuprofen may need additional doses of activated charcoal. This study supports the targeted use of activated charcoal in colchicine, hydroxychloroquine, ibuprofen, and strychnine ingestions. Isotherm modeling reveals xenobiotic-specific differences in adsorption efficiency that may inform clinical decisions regarding dose, timing, and the potential use of additional charcoal administration.
2025-02-19 | Pumpkin seeds oil rescues colchicine-induced neurotoxicity in rats via modifying oxidative stress, DNA damage, and immunoexpression of BDNF and GFAP.
Colchicine (CHC), a poisonous plant alkaloid, has been widely utilized for decades in the treatment of gout, but has a rather low therapeutic index, which causes oxidative stress leading to cognitive impairment, brain damage, apoptosis, and hitopathological alterations in humans and experimental animals. The present investigation evaluated the potential palliative effect of the pumpkin seeds oil (PSO) at a dose of 4 ml/kg b.wt against CHC (0.6 mg/kg b.wt) -induced neurotoxic and neurobehavioral effects in rats. Forty male rats weighing 245-260 g were assigned to four groups. The results displayed that CHC exposure induced neurobehavioral disorders and a remarkable decline in the serotonin and dopamine levels and the immunoexpression of BDNF and GFAP in the brain. Besides, CHC treatment evoked brain oxidative stress, as manifested by depleted antioxidant enzyme activities and elevated malondialdehyde (MDA) and protein carbonyl (PC) levels. Also, CHC triggered brain DNA damage, as indicated by a marked increment in the brain 8-Hydroxyguanosine (8-OHdG) level. However, concurrent treatment with the PSO effectively attenuated the CHC-induced toxic effects as evidenced by a noticeable increase in the serotonin (33 ± 3.05) and dopamine (2.48 ± 0.40) concentrations, and the BDNF and GFAP immunoexpression in the brain. Moreover, PSO mitigated CHC-induced brain oxidative stress and DNA damage as shown by elevated antioxidant enzyme activities (164 ± 3.46 SOD and 7.55 ± 0.43 CAT) and reduced MDA (1.62 ± 0.23), PC (1.35 ± 0.23), and 8-OHdG (3.02 ± 0.33) levels. These results concluded that PSO could serve as a therapeutic strategy to ameliorate the neurotoxic and neurobehavioral impacts of CHC.
2025-01-27 | WCN25-3435 SUCCESSFUL MANAGEMENT OF COLCHICINE TOXICITY-INDUCED MULTI-ORGAN FAILURE THROUGH CONTINUOUS RENAL REPLACEMENT THERAPY
Colchicine, is a well-known treatment for gout and pericarditis, but its narrow therapeutic window poses a significant risk for toxicity, even at therapeutic doses. We present the case of a woman who suffered a severe colchicine poisoning resulting in multi-organ failure, including acute kidney injury (AKI), and her complete recovery following renal replacement therapy.
2024-11-21 | Comprehensive multi-omics analysis elucidates colchicine-induced toxicity mechanisms and unveils the therapeutic potential of MLN4924 and kinase inhibitors.
Colchicine is a widely prescribed anti-inflammatory drug for the treatment of gout, familial Mediterranean fever and pericarditis, but its narrow therapeutic window presents a significant risk of severe toxicity. Despite its clinical relevance, the molecular mechanisms underlying colchicine's pharmacological effects and associated toxicity and explored potential therapeutic interventions to mitigate its adverse effects. We showed the colchicine's impact on cellular morphology in human umbilical vein endothelial cells (HUVEC) and HeLa cells including cell rounding and detachment following 24 h of exposure that revealed pronounced cytotoxic effects. We then established a large-scale screening model to identify small molecules capable of reversing colchicine-induced cellular toxicity, and identified MLN4924, an inhibitor of the Cullin-RING E3 ligase (CRL) system, as a promising candidate for mitigating colchicine-induced cellular injury. Through a comprehensive multi-omics approach including transcriptomics, proteomics, phosphoproteomics and ubiquitinomics, we systematically characterized the molecular perturbations caused by colchicine and delineated the protective mechanisms of MLN4924. We found that MLN4924 exerted its protective effects by modulating critical cellular pathways, specifically preventing the dysregulation of cell cycle progression, mitotic disruption and microtubule destabilization triggered by colchicine. Furthermore, proteomic and phosphoproteomic analyses revealed significant alterations in kinase signaling networks, with combined inhibition of CDK1 and PAK1 emerging as an effective strategy to counteract colchicine-induced cellular dysfunction. These results not only provide a detailed molecular characterization of colchicine toxicity but also identify key therapeutic targets, laying the groundwork for the development of targeted interventions to mitigate colchicine-induced adverse effects in clinical practice.
proteins
2025-10-29 | Successful multimodal intensive care management including early plasmapheresis and granulocyte colony stimulating factor in severe colchicine poisoning: A case report.
Colchicine is a narrow therapeutic index drug widely used in the treatment of inflammatory diseases such as acute gout attacks and Familial Mediterranean Fever (FMF). In case of overdose, the risk of toxicity is high and can rapidly lead to multiple organ failure. The lack of an antidote for colchicine toxicity continues the search for a definitive treatment. We present a case of severe colchicine toxicity managed successfully with early initiation of therapeutic plasma exchange (TPE), intensive supportive care including noninvasive ventilation, hemodynamic stabilization, electrolyte management, and granulocyte colony- stimulating factor (G-CSF) therapy. This multimodal intensive care approach resulted in complete recovery.
2023-08-16 | Drastic alterations in the loop structure around colchicine upon complex formation with an engineered lipocalin indicate a conformational selection mechanism
Using Anticalin technology, a lipocalin protein dubbed Colchicalin, with the ability to bind the toxic plant alkaloid colchicine with picomolar affinity, has previously been engineered, thus offering a potential antidote in vivo and also allowing its sensitive detection in biological samples. To further analyze the mode of ligand recognition, the crystal structure of Colchicalin is now reported in its unliganded form and is compared with the colchicine complex. A superposition of the protein structures revealed major rearrangements in the four structurally variable loops of the engineered lipocalin. Notably, the binding pocket in the unbound protein is largely occupied by the inward-bent loop #3, in particular Ile97, as well as by the phenylalanine side chain at position 71 in loop #2. Upon binding of colchicine, a dramatic shift of loop #3 by up to 11.1 Å occurs, in combination with a side-chain flip of Phe71, thus liberating the necessary space within the ligand pocket. Interestingly, the proline residue at the neighboring position 72, which arose during the combinatorial engineering of Colchicalin, remained in a cis configuration in both structures. These findings provide a striking example of a conformational adaptation mechanism, which is a long-known phenomenon for antibodies in immunochemistry, during the recognition of a small ligand by an engineered lipocalin, thus illustrating the general similarity between the mode of antigen/ligand binding by immunoglobulins and lipocalins.
2023-06-01 | In vivo neutralization of colchicine toxicity by a PASylated anticalin in a rat model.
We have investigated the pharmacokinetics (PK) and in vivo activity of an Anticalin exhibiting picomolar affinity towards colchicine, a plant toxin with low tolerable dose in humans. PK analysis of the 20-kDa "Colchicalin" protein in male Sprague Dawley rats (n = 3) revealed a very short plasma half-life (3.5 min), which was prolonged 21-fold via genetic fusion with a 200-residue Pro/Ala sequence (PASylation). The scavenging activity of the PASylated Colchicalin was investigated over 3.5 h via stoichiometric application following a sub-toxic i.v. dose of colchicine on anesthetized rats (n = 2) leading to a rapid rise in total plasma colchicine concentration. We then established a 14-day intoxication model in rats (n = 3) at a 30 mg/kg p.o. colchicine dose which was characterized by severe weight loss, elevated neutrophil-to-lymphocyte ratio and shortened survival. PASylated Colchicalin administration at 4.2% of the neutralizing dose (125 mg/kg/day daily for 12 consecutive days) resulted in faster relief of the symptoms in 2/3 of animals (n = 6) compared to the control group without Colchicalin treatment (n = 5). Nevertheless, 1/3 of the rats died suddenly after the first Colchicalin injection, probably due to a steep rise in the total colchicine plasma concentration, which suggests further improvement of the dosing scheme prior to potential application in acute human colchicine poisoning.
2021-07-29 | Pathogenic characteristics and treatment in 43 cases of acute colchicine poisoning
Abstract Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5–0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries， include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration.
2021-05-12 | Poisoning with Soranjan (Colchicum): a case report
Introduction: Colchicine, which is derived from a herb called Colchicum is a medication used to treat gout. Colchicum itself can act as a deadly toxic herb in the case of over dose. This is a case report study which investigates a patient who was poisoned with Colchicum (Soranjan, what it is called in Iran). Description: The patient was a 44-year-old man who came to the emergency poisoning ward after a day of mountaineering and eating Soup. He had severe nausea and vomiting. The patient was admitted to the ICU two days later with a toxic general condition, complaining of chest pain, nausea, vomiting and shortness of breath. The patient lab tests showed elevated liver enzymes and pancytopenia. The patient respiratory distress developed and physician had to intubate the patient. The patient was treated with antibiotics, GCSF for pancytopenia and antioxidant to protect the liver. Conclusion: The patient responded to broad spectrum antibiotic, antifungal and GCSF. paying attention to the patient’s history was the key of success to diagnosis.
cell therapies
2026-05-06 | A large pediatric cohort of colchicine intoxication: prognostic factors and experience with rapid sequence apheresis.
Severe colchicine intoxication often leads to multi-organ failure and death. With no specific antidote and ineffective conventional elimination methods, we hypothesized that rapid sequence apheresis could reduce the intravascular colchicine reservoir. This study describes pediatric colchicine poisoning, focusing on dose-related outcomes and the clinical role of rapid sequence apheresis. This retrospective observational analysis included children admitted to a tertiary pediatric intensive care unit for colchicine poisoning (2011-2025). Clinical data, ingested dose, organ involvement, and patient characteristics were evaluated. Logistic regression and ROC analyses were used to identify variables associated with disease severity and poor outcomes, including those treated with rapid sequence apheresis. Eighty-four patients were included (median dose: 0.3 mg/kg). Across dose groups (<0.5, 0.5-0.8, and >0.8 mg/kg), higher doses correlated with increased frequency of diarrhea (20.6%, 57.1%, and 57.1%, respectively, P = 0.071) and cardiovascular involvement (20.6%, 50%, and 71.4%, respectively; P = 0.004). Logistic regression showed that diarrhea significantly increased the likelihood of cardiovascular complications (OR: 3.24, P = 0.006). The ROC analysis identified thresholds of >0.39 mg/kg and >24 mg total dose as predictors of cardiovascular toxicity. Seventeen patients (20.2%) underwent rapid sequence apheresis. Despite advanced supportive care, five patients died, including two who ingested <0.5 mg/kg and received rapid sequence apheresis. Our findings suggest that higher ingested doses and early gastrointestinal manifestations such as diarrhea may serve as indicators of increased risk for cardiovascular complications in pediatric colchicine intoxication. In addition, clinically significant toxicity may occur at doses lower than traditionally reported thresholds. Pediatric colchicine intoxication may lead to significant cardiovascular complications even at relatively lower doses. Early recognition of high-risk clinical indicators, including gastrointestinal symptoms, leukocytosis, and ingested dose, may facilitate clinical risk stratification and early identification of patients at increased risk of adverse outcomes. Rapid sequence apheresis was used in selected severe cases in our cohort; however, its therapeutic role requires further investigation.
2022-10-03 | Colchicine Poisoning Cases in a Pediatric Intensive Care Unit: A Twenty-Year Study.
Colchicine intoxication is rare but potentially fatal. The toxic dose of colchicine is not well established; it has been reported that major toxicity starts after doses of 0.5 mg/kg. We aimed to evaluate the demographic, clinical aspects, treatments, and outcome of colchicine toxicity cases in the pediatric intensive care unit (PICU). We collected the data of patients aged between 0 and 18 years, admitted to Ankara University Faculty of Medicine PICU for colchicine poisoning (n = 22), from October 1999 to January 2020, retrospectively. Data extracted from the cases included age, sex, chronic condition, time between intake of drug and admission to PICU, source of drug, amount of drug ingested, other drug intake, symptoms, clinical findings, cardiac involvement, laboratory results, time of stay in PICU, treatment, and outcome. Patients' age ranged from 7 months to 17 years. Median age was 86 months. The most common symptom at time of admission was vomiting, occurring in 13 (59%) of the patients. Two of the patients presented with change in mental status. Time between taking medication and applying to the hospital ranged from half an hour to 4 days. Medication intake of 3 of 22 patients was more than 0.5 mg/kg. One patient whose parents' best estimate of dose ingested was 0.48 mg/kg died because of the development of multiorgan failure. One patient who ingested 0.4 mg/kg of colchicine underwent plasma exchange and recovered without any complications. Colchicine poisoning has a high risk of mortality, and death can be seen in doses less than a single acute dose of 0.5 mg/kg. These patients need close monitoring because there is always a risk of them to require aggressive support. Prognosis is poor in patients who have rapidly developing hemodynamic failure.
2019-01-01 | Plasmapheresis in Acute Intoxication and Poisoning
The chapter will: Present an overview of the possible mechanisms of action of plasmapheresis in poisoning and drug overdose. Review the pharmacokinetic factors that affect the elimination of poisons/drugs by plasmapheresis. Highlight the limitations of published studies on the efficacy of plasmapheresis in poisoning and drug overdose. Summarize published data on the efficacy of plasmapheresis for specific poisons and drugs.
2014-09-26 | Plasma Exchange Treatment in a Case of Colchicine Intoxication
Therapeutic Apheresis and DialysisVolume 19, Issue 1 p. 95-97 Letter to the Editor Plasma Exchange Treatment in a Case of Colchicine Intoxication Demet Demirkol, Demet Demirkol Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorBurcin N Karacabey, Burcin N Karacabey bnazlikaracabey@hotmail.com Department of Pediatrics, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorFatih Aygun, Fatih Aygun Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this author Demet Demirkol, Demet Demirkol Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorBurcin N Karacabey, Burcin N Karacabey bnazlikaracabey@hotmail.com Department of Pediatrics, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this authorFatih Aygun, Fatih Aygun Department of Pediatric Intensive Care, Bezmialem Vakif University, Istanbul, TurkeySearch for more papers by this author First published: 26 September 2014 https://doi.org/10.1111/1744-9987.12226Citations: 14Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume19, Issue1February 2015Pages 95-97 RelatedInformation
2014-05-01 | ABSTRACT 795
Background and aims: Colchicine poisoning is an uncommon, but potentially life-threatening, toxicologic emergency. It has a narrow therapeutic index and even death can be occur in minor toxicity. Initial 36 to 72 hours after ingestion, death might be seen caused by hypovolemic shock, central nervous system damage, and cardiopulmonary insufficiency. All patients who had colchicine overdose should be followed and treated in the intensive care units and treatment is usually supportive. Aims: In this case, we presented a patient diagnosed as colchicine intoxication and treated with plasma exchange. Methods: A previously healthy 6-year-old girl was ingested lethal doses of colchicium and referred to our pediatric intensive care unit (PICU). During the admission she had acute respiratory distress syndrome (ARDS), elevated transaminase levels, diarrhea and coagulopathy. The two plasma exchange session were applied to the patient who had multiorgan insufficiency already. Results: Drug removal during plasmapheresis are sparse, -mostly case reports of overdoses have described the effects of plasmapheresis on pharmaceutical. In general, drugs with a low volume of distribution (Vd) and/or a high rate of protein binding are most likely to be removed during plasma exchange. Colchicine completely does not have these features. But in some cases, plasma exchange might be beneficial in the treatment of colchicine intoxications. Conclusions: As a result, we consider that plasma exchange can be beneficial in eradication of colchicine from the body as it tightly binds to the plasma proteins and also decrease the mortality caused by its intoxication.
antibodies
2022-08-19 | Ku70 affects the frequency of chromosome translocation in human lymphocytes after radiation and T-cell acute lymphoblastic leukemia
Abstract Background As one of the most common chromosomal causes, chromosome translocation leads to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of error-prone DNA repair and it may end in translocation. So far, the direct correlation between Ku70 and translocation has not been assessed. This study aimed to investigate the association between Ku70 and translocation in human lymphocytes after radiation and T-ALL. Methods Peripheral blood lymphocytes (PBLs) from volunteers and human lymphocyte cell line AHH-1 were irradiated with X-rays to form the chromosome translocations. Phytohemagglutinin (PHA) was used to stimulate lymphocytes. The frequency of translocation was detected by fluorescence in situ hybridization (FISH). Meanwhile, the expression of Ku70 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Furthermore, Ku70 interference, overexpression and chemical inhibition were used in AHH-1 cell lines to confirm the correlation. Finally, the expression of Ku70 in T-ALL samples with or without translocation was detected. Results The expression of Ku70 and frequencies of translocation were both significantly increased in PBLs after being irradiated by X-rays, and a positive correlation between the expression (both mRNA and protein level) of Ku70 and the frequency of translocation was detected (r = 0.4877, P = 0.004; r = 0.3038, P = 0.0358 respectively). Moreover, Ku70 interference decreased the frequency of translocations, while the frequency of translocations was not significantly affected after Ku70 overexpression. The expression of Ku70 and frequencies of translocation were both significantly increased in cells after irradiation, combined with chemical inhibition ( P < 0.01). The protein level and mRNA level of Ku70 in T-ALL with translocation were obviously higher than T-ALL with normal karyotype ( P = 0.009, P = 0.049 respectively). Conclusions Ku70 is closely associated with the frequency of chromosome translocation in human lymphocytes after radiation and T-ALL. Ku70 might be a radiation damage biomarker and a potential tumor therapy target.
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Drug Discovery Landscape
1 orphan drug designation for Colchicine poisoning.
1 orphan drug designation for Colchicine poisoning.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ovine anti-colchicine polyclonal antibody fragments [COLCHIFAB] | antibodies | EMA | 2010-12-17 | — | Serb |
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