Role Of Colchicine Research Articles

Is There a Role for Colchicine in the Treatment of Oral Mucous Membrane Pemphigoid?

Is There a Role for Colchicine in the Treatment of Oral Mucous Membrane Pemphigoid?

The role of colchicine on ventricular remodelling following myocardial infarction and ischemia-reperfusion injury: article review

Acute myocardial infarction (AMI) is a major cause of cardiac dysfunction, arrhythmias, and a poor prognosis. Even though new technologies have been developed to aid in opening the culprit coronary artery and correcting ischemia-related stenosis by percutaneous coronary intervention (PCI), the ventricular remodelling that induces cardiac failure as a consequence of AMI remains unchanged. Colchicine, a versatile anti-inflammatory medication, has been documented in mitigating cardiac remodelling and enhancing cardiac function following AMI. This article provides an in-depth review of the processes by which colchicine affects ventricular remodeling after AMI, highlighting the potential role of inflammation in the pathogenesis and progression of ventricular dysfunction. Keyword: Colchicine, Ischemia-Reperfusion Injury, Myocardial Infarction, Ventricular Remodelling

Role of Colchicine in Cardiovascular Disorders.

Inflammation has played a pivotal role in atherosclerosis and other cardiovascular disorders, prompting the exploration of anti-inflammatory therapies to improve cardiovascular outcomes. Colchicine, a well-established agent in conditions such as gout and familial Mediterranean fever, has emerged as a promising novel anti-inflammatory agent in the realm of cardiovascular diseases. Its ability to target both traditional risk factors and residual inflammatory risk marks a significant advancement in cardiovascular prevention strategies, indicating a new era in cardiovascular care. Landmark trials have supported the efficacy and safety of low-dose colchicine in reducing major adverse cardiovascular events when combined with standard therapies. In addition, its endorsement by major cardiovascular societies underscores its significance as the first targeted anti-inflammatory therapy for cardiovascular disease. However, careful monitoring for drug interactions and adverse effects, particularly on kidney and liver function, is essential for safe use. In this review, we aim to comprehensively summarize the mechanisms of action of colchicine, its molecular and biochemical targets in various cardiovascular conditions, and its pharmacokinetics, and delve deeply into the existing evidence on its safety and efficacy in the treatment of cardiovascular disorders, including coronary artery disease, pericarditis, atrial fibrillation, and heart failure.

The role of colchicine in the management of COVID-19: a Meta-analysis

BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has robustly affected the global healthcare and economic systems and it was caused by coronavirus-2 (SARS-CoV-2). The clinical presentation of the disease ranges from a flu-like illness to severe pneumonia and death. Till September 2022, the cumulative number of cases exceeded 600 million worldwide and deaths were more than 6 million. Colchicine is an alkaloid drug that is used in many autoinflammatory conditions e.g., gout, familial Mediterranean fever, and Behçet’s syndrome. Colchicine inhibits the production of superoxide and the release of interleukins that stimulate the inflammatory cascade. Colchicine decreases the differentiation of myofibroblast and the release of fibrotic mediators including transforming growth factor (TGF-β1) that are related to the fibrosis. Moreover, colchicine has been used to traet viral myocarditis caused by CMV or EBV, interstitial pneumonia, and pericarditis resulting from influenza B infection. Additionally, colchicine is considered safe and affordable with wide availability.ObjectiveThe aim of the current study was to assess the evidence of colchicine effectiveness in COVID-19 treatment.MethodsA comprehensive review of the literature was done till May 2022 and yielded 814 articles after ranking the articles according to authors and year of publication. Only 8 clinical trials and cohort studies fulfilling the inclusion criteria were included for further steps of data collection, analysis, and reporting.ResultsThis meta-analysis involved 16,488 patients; 8146 patients in the treatment group and 8342 patients in the control group. The results showed that colchicine resulted in a significant reduction in the mortality rate among patients received colchicine in comparison with placebo or standard care (RR 0.35, 95%CI: 0.15–0.79). Colchicine resulted in a significant decrease in the need for O2 therapy in patients with COVID-19 (RR 0.07, 95%CI 0.02–0.27, P = 0.000024). However, colchicine had no significant effect on the following outcomes among COVID-19 patients: the need for hospitalization, ICU admission, artificial ventilation, and hospital discharge rate. Among the PCR confirmed COVID-19 patients, colchicine decreased the hospitalization rate (RR 0.75, 95%CI 0.57–0.99, P = 0.042). However, colchicine had no effect on mortality and the need for mechanical ventilation among this subgroup.ConclusionColchicine caused a significant clinical improvement among COVID-19 patients as compared with the standard care or placebo, in terms of the need for O2, and mortality. This beneficial effect could play a role in the management of COVID-19 especially severe cases to decrease need for oxygen and to decrease mortality among these patients.

Analysis of clinical manifestations and spectrum of pharmacotherapy in Moscow and St. Petersburg cohorts of patients with adult-onset Still's disease

Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease of unknown etiology characterized by clinical manifestations such as fever, non-stable maculopapular rash, arthritis and/or arthralgias and leukocytosis with neutrophilia.Objective: to analyze the spectrum of clinical manifestations of AOSD and pharmacotherapy in real clinical practice.Material and methods. A cross-sectional study included 111 patients with a confirmed diagnosis of AOSD according to the Yamaguchi criteria, who were treated in two large Russian centers from 2019 to 2022: V.A. Nasonova Research Institute of Rheumatology (Moscow) and Almazov National Medical Research Centre (Saint Petersburg).Results and discussion. We analyzed the spectrum of clinical manifestations throughout the course of the disease. The spectrum of clinical manifestations of AOSD in our study was shown to be similar to the results of other studies. It was found that the frequency of the different clinical manifestations did not differ significantly.The majority of patients (74%) in our cohort received glucocorticosteroids (GC) in combination with disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs (bDMARDs). Monotherapy with GC was used in only 9% of patients. Up to 80% of patients received methotrexate (MTX) at various stages of the disease. For the treatment of patients refractory to GC and MTX therapy, bDMARDs were prescribed (44% of cases), most frequently interleukin-6 inhibitors (34%). In the St. Petersburg cohort, 13 (31.7%) of 41 patients were taking colchicine, which enabled control of disease manifestations and a reduction in the need for GC in 9 of them.Conclusion. Thus, we can draw a preliminary conclusion about the presence of steroid dependence in patients with AOSD. Up to 79.3% of AOSD patients are forced to take GC for a long period of time, which is associated with the risk of complications. Further studies on the optimal profile of bDMARDs are needed, as well as the role of colchicine as a potential therapeutic option for certain clinical and immunological subtypes of AOSD.

Update on the Role of Colchicine in Cardiovascular Disease.

This review focuses on the use of colchicine to target inflammation to prevent cardiovascular events among those at-risk for or with established coronary artery disease. Colchicine is an anti-inflammatory drug that reduces cardiovascular events through its effect on the IL-1β/IL-6/CRP pathway, which promotes the progression and rupture of atherosclerotic plaques. Clinical trials have demonstrated that colchicine reduces cardiovascular events by 31% among those with chronic coronary disease, and by 23% among those with recent myocardial infarction. Its ability to dampen inflammation during an acute injury may broaden its scope of use in patients at risk for cardiovascular events after major non-cardiac surgery. Colchicine is an effective anti-inflammatory therapy in the prevention of acute coronary syndrome. Ongoing studies aim to assess when, and in whom, colchicine is most effective to prevent cardiovascular events in patients at-risk for or with established coronary artery disease.

Is Colchicine the New “Aspirin”?

For more than six decades, ischemic heart disease has sustained as the world’s leading cause of death. Growing evidence suggests chronic inflammation as the underlying pathophysiology of this illness. Due to this, inflammatory markers have become a mainstay of diagnosing, prognosticating, and following up the effectiveness of therapy. Colchicine remains a contentious treatment option for coronary heart disease, despite mounting evidence to the contrary from recent studies. This article discusses the basics of inflammation, the role of colchicine, various clinical studies, and the latest guidelines on colchicine. Colchicine has the potential to develop into a cheap, novel, and effective therapy for coronary artery disease.

Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway

BackgroundCoronary microembolization(CME)is a common complication in acute coronary syndrome and percutaneous coronary intervention, which is closely related to poor prognosis. Pyroptosis, as an inflammatory programmed cell death, has been found to be associated with CME-induced myocardial injury. Colchicine (COL) has potential benefits in coronary artery disease due to its anti-inflammatory effect. However, the role of colchicine in pyroptosis-related CME-induced cardiomyocyte injury is unclear. This study was carried out to explore the effects and mechanisms of colchicine on myocardial pyroptosis induced by CME.MethodsThe CME animal model was constructed by injecting microspheres into the left ventricle with Sprague-Dawley rats, and colchicine (0.3 mg/kg) pretreatment seven days before and on the day of modeling or compound C(CC)co-treatment was given half an hour before modeling. The study was divided into 4 groups: Sham group, CME group, CME + COL group, and CME + COL + CC group (10 rats for each group). Cardiac function, serum myocardial injury markers, myocardial histopathology, and pyroptosis-related indicators were used to evaluate the effects of colchicine.ResultsColchicine pretreatment improved cardiac dysfunction and reduced myocardial injury induced by CME. The main manifestations were the improvement of left ventricular systolic function, the decrease of microinfarction area, and the decrease of mRNA and protein indexes related to pyroptosis. Mechanistically, colchicine increased the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK), promoted the expression of silent information regulation T1 (SIRT1), and inhibited the expression of NOD-like receptor pyrin containing 3 (NLRP3) to reduce myocardial pyroptosis. However, after CC co-treatment with COL, the effect of colchicine was partially reversed.ConclusionColchicine improves CME-induced cardiac dysfunction and myocardial injury by inhibiting cardiomyocyte pyroptosis through the AMPK/SIRT1/NLRP3 signaling pathway.

Inflammation, anti-inflammatory agents, and the role of colchicine in carotid artery stenosis.

Cardiovascular disease is a major cause of morbidity and mortality worldwide. In the last few years, the role of inflammation and inflammatory modulatory medications is investigated for the optimal treatment of coronary artery disease. It can be hypothesized that since inflammation is also involved in carotid artery stenosis development and progression, the same class of medication could be useful. Our objective with this review is to present the available evidence, published studies and promising ongoing trials on the role of anti-inflammatory medications - with a special emphasis on the most commonly used drug of this class: colchicine - in patients with carotid artery stenosis.

Unlocking Colchicine's Untapped Potential: A Paradigm Shift in Hepatocellular Carcinoma Prevention.

Background: Liver cancer and notably hepatocellular carcinoma (HCC), results in significantly high mortality rates worldwide. Chronic hepatitis and fatty liver, recognized precursors, underscore the imperative need for effective preventive strategies. This study explores colchicine, traditionally acknowledged for its anti-inflammatory properties and investigates its potential in liver cancer prevention. Methods: Utilizing the iHi Data Platform of China Medical University Hospital, Taiwan, this study analyzed two decades of medical data, incorporating 10,353 patients each in the Colchicine and Non-Colchicine cohorts, to investigate the association between colchicine use and liver cancer risk. Results: The study identified that colchicine users exhibited a 19% reduction in liver cancer risk, with a multivariable-adjusted odds ratio of 0.81 after accounting for confounding variables. Additionally, the influence of gender and comorbidities like diabetes mellitus on liver cancer risk was identified, corroborating the existing literature. A notable finding was that the prolonged use of colchicine was associated with improved outcomes, indicating a potential dose-response relationship. Conclusions: This study proposes a potential new role for colchicine in liver cancer prevention, extending beyond its established anti-inflammatory applications. While the findings are promising, further research is essential to validate these results. This research may serve as a foundation for future studies, aiming to further explore colchicine's role via clinical trials and in-depth investigations, potentially impacting preventive strategies for liver cancer.

Role of Colchicine in Reduction of No Reflow Phenomenon in Patients with Acute ST-Segment Myocardial Infarction, Undergoing Primary Percutaneous Coronary Intervention

Abstract Aim and objectives The aim of this work is to study the efficacy of colchicine administration as a preventive tool for No Reflow in patients with STEMI undergoing primary PCI. Patients and Methods The study included 100 patients who presented with acute STEMI to the cardiology department of Ain Shams university hospitals and underwent primary PCI (percutaneous coronary intervention). They were divided into two groups where the first group received colchicine (1 mg) besides guideline recommended therapy before primary PCI and the 2nd group served as a control group and received guideline recommended therapy. Post interventional thrombolysis in myocardial infarction (TIMI) flow grade and myocardial blush grade (MBG) were recorded. Results The majority of patients in both groups had the LAD as the culprit vessel for their presentation(63%). In the control group there were 19 patients with TIMI flow less than 3 and 20 patients with MBG less than 3. Meanwhile in the cases group there was 8 patients with TIMI flow less than 3 and 7 patients with MBG less than 3. This difference was statistically significant with a P value of 0.013. There were 40 patients in the cases group who received loading clopidogrel (600 mg) as premedications before Primary PCI (80%) vs 25 patients (50%) in the control group which was statistically highly significant with a P value of 0.002. In addition, Intracoronary medications (adrenaline, verapamil, tirofiban that where given during the procedure) used in 2 patients from the cases group vs 10 from the control group which was statistically significant with a P value of 0.014. There was not a statistically significant difference between the two groups regarding presenting balloon dilatation. Whereas, Post stenting balloon dilatation showed a statistically significant relationship of P value 0.014 which was done in 2 patients from the cases group vs 10 patients from the control group. Conclusion Colchicine loading before primary PCI resulted in improved postprocedural TIMI flow, MBG.

Benefits of Low Dosage of Colchicine Administration on Decreasing Rehospitalization and Mortality within 30 Days in Post-Acute Coronary Syndrome Patients with ST-Segment Elevation Undergoing Percutaneous Coronary Intervention

Background: The role of inflammation in myocardial infarction and post-infarction MI remodeling has become a concern for the development of treatment in the last decade. Colchicine can prevent increased inflammation during acute injury. Objective: This study focused on the role of colchicine as an on-top medical treatment, hoping it can reduce mortality and short-term rehospitalization in patients with STEMI. Methods: 347 AMI patients (18-80 year old adults) who visited RSUD dr. Saiful Anwar Malang, between February 2022 and January 2023, participated in this prospective, randomized, double-blinded, placebo-controlled experiment. Patients were split into two groups and given either a placebo or colchicine 0.5 mg daily for a month. Standard medical therapy was administered concurrently to both groups as an approachable guideline. The study endpoints were mortality and rehospitalization rates. Result: After one month of follow-up, there was a reduction in rehospitalization due to cardiovascular causes (2 [1.3%] vs. 4 [2.7%], HR 3.42 [1.36-8.56], p<0.05), which was significant in the treatment group compared to the control group. Also, there was a reduction in all-cause mortality, but not statistically significant (2 [1,3% v 3 [2,0%], HR 3,38 [0,53-7,48], p>0,05). In the treated group, there was also a lower non-cardiovascular rehospitalization rate compared to placebo, but not significant (4 [2.6%] vs. 7 [4.7], HR 0.42 [0.15-1.02], p<0.05). Conclusion: The administration of low-dose colchicine for one month has shown benefits in reducing rehospitalization in patients with STEMI who receive PCI therapy.

Colchicine in Cardiovascular Diseases

Colchicine has been used since ancient times for gout and familial Mediterranean fever. Inflammation plays a major role in the pathogenesis of atherosclerosis thus paving a way for the use of anti-inflammatory drugs in the management of cardiovascular diseases (CVD). The role of colchicine in the management of pericarditis has been well established. It has been evident from clinical trials the beneficial effects of colchicine in various cardiovascular conditions such as coronary artery disease, atrial fibrillation, and postcardiotomy syndromes. The most frequently used dose of colchicine is 0.5 mg once a day, with duration varying according to clinical condition. The widespread availability, low cost and acceptable side effect profile has made colchicine an attractive therapeutic option. The aim of this article is to summarize colchicine’s mechanism of action and evidence from various trials of its use in CVD in the current era.

Kembang sungsang (Gloriosa superba L.): A potential plant as a source of biomutagens

Gloriosa superba (Kembang Sungsang, local name) belongs to the monocotyledoneae class and the Liliaceae family. This plant is known as a medicinal plant and its pharmacological effects have been developed both traditional and modern. All parts of the Gloriosa superba, especially the tubers and seeds, contain alkaloids namely colchicine and gloriosine. The content of colchicine and colchicides in tubers and other parts of plants is about 0.1 - 0.9% and 0.8% respectively. Colchicine has a strong affinity for tubulin so it is often used in biological studies and plant breeding to induce mutations that produce polyploidy individuals. Colchicine as a mutagen is used to develop the superior properties of some plants. Polyploidi plants have several advantages including larger cells, higher plants, wider leaves, larger fruits, higher production, and plants becoming more resistant to disease. Considering the role of colchicine above, the prospect of Gloriosa superba as a source of biomutagens (natural colchicine) needs to be studied and further developed.

The Role of Colchicine in Atherosclerosis: From Bench to Bedside.

Inflammation is a key feature of atherosclerosis. The inflammatory process is involved in all stages of disease progression, from the early formation of plaque to its instability and disruption, leading to clinical events. This strongly suggests that the use of anti-inflammatory agents might improve both atherosclerosis progression and cardiovascular outcomes. Colchicine, an alkaloid derived from the flower Colchicum autumnale, has been used for years in the treatment of inflammatory pathologies, including Gout, Mediterranean Fever, and Pericarditis. Colchicine is known to act over microtubules, inducing depolymerization, and over the NLRP3 inflammasome, which might explain its known anti-inflammatory properties. Recent evidence has shown the therapeutic potential of colchicine in the management of atherosclerosis and its complications, with limited adverse effects. In this review, we summarize the current knowledge regarding colchicine mechanisms of action and pharmacokinetics, as well as the available evidence on the use of colchicine for the treatment of coronary artery disease, covering basic, translational, and clinical studies.

Role of colchicine in the management of COVID-19 patients: A meta-analysis of cohort and randomized controlled trials

BackgroundColchicine is well known drug for the treatment of acute gout. Recently, it has also been used in the management of COVID-19 patients. AimThe aim of current study is to find out the role of colchicine in COVID-19 patients. Material & methodsThe relevant studies were searched in PubMed/Medline, Google scholar and clinical trail.gov.com till inception and sorted based on the inclusion and exclusion criteria. The quality assessment of studies were done using Newcastle Ottawa Quality Assessment Scale. The pooled estimate was calculated as odd ratio and pooled prevalence with 95% confidence interval. A random effect model was used and publication bias was assessed qualitatively by trim and fill method. ResultsOut of 38 studies, a total of 6 studies were found relevant for the analysis containing 1146 patients (705 males and 441 females). The pooled odd ratio was found to be 0.35 [0.23, 0.53] which indicate significance reduction of mortality in colchicine group as compared to non-colchicine group. The pooled prevalence of the patients treated with colchicine were found to be significant [0.11(0.03, 0.24)]. The heterogeneity among studies was also found to be low (I2 = 11%). However, funnel plot has indicated the involvement of publication bias [Egger: bias = 10.168291 (95% CI = 5.042044 to 15.294537) P = 0.0053]. ConclusionColchicine might be helpful in reduction of mortality in the management of COVID-19 patients. However, further studies are required to confirm its exact role.

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial

Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020).

Anti-inflammatory effects of colchicine on coronary artery disease

Inflammation plays a crucial role in the pathophysiology of coronary artery disease (CAD). Several types of sterile inflammation are mediated through the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Colchicine has recently been shown to effectively block NLRP3 inflammasome assembly in addition to several other actions on inflammatory cells. Recent evidence also points to favorable effects of colchicine in patients with CAD, including lower levels of inflammatory markers, coronary plaque stabilization, and more favorable cardiac recovery after injury. This review focuses on the role of colchicine in the process of atherosclerosis and discusses its potential as a therapeutic option for the prevention and treatment of CAD.

Role of Colchicine in Management of COVID-19?

CoV-2 disease 2019 (COVID-19) pandemic has exerted a great burden on the health and economic systems worldwide. One of the most important factors that affect the severity and prognosis of COVID-19 is the occurrence of hyperstimulation of the immune system resulting in “cytokine storm”. Similar to SARS-CoV, an intracellular complex called nod like receptor family pyrin domain containing 3 (NLRP3) inflammasome was found to be activated by SARS-CoV-2, then in turn stimulates several interleukins and initiates the inflammatory cascade. In addition, other inflammatory mediators such as interferons e.g., IFN-α, and IFN-γ, interleukins e.g., IL-1β, IL-12, IL-18, tumor necrosis factor-α (TNF- α), and chemokines e.g., CCL2, CXCL10 have been reported in severely ill patients. These mediators represent the corner stone in developing cytokine storm that results in uncontrolled systemic inflammatory reaction with subsequent acute respiratory distress syndrome (ARDS), multiple organ failure and eventually death. Based on its anti-inflammatory effects, colchicine has also gained attention to be utilized in the management of COVID-19 patient. Colchicine exerts its anti-inflammatory effect through inhibition of formation of microtubules which is considered an essential step in several cellular processes such as division, signalling, and migration. Also, colchicine affects the cytokine cascade by inhibiting IL-1β leading to reduction in neutrophils recruitment, free radicles production and inflammasome stimulation. This raises the concerns about the effectiveness of colchicine in COVID-19 treatment and the possibility of providing an improvement of the clinical course of the disease.

Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine.

In 2020, SARS-COV-2 put health systems under unprecedented resource and manpower pressure leading to significant number of deaths. Expectedly, researchers sought to shed light on the pathophysiologic background of this novel disease (COVID-19) as well as to facilitate the design of effective therapeutic modalities. Indeed, early enough the pivotal role of inflammatory and thrombotic pathways in SARS-COV-2 infection has been illustrated. The purpose of this article is to briefly present the epidemiologic and clinical features of COVID-19, analyze the pathophysiologic importance of immunologic dysregulation and hypercoagulability in developing disease complications and finally to present an up-to-date systematic review of colchicine’s immunomodulating capacity in view of hindering coronavirus complications.