Colchicine as an anti-inflammatory and cardioprotective agent.
Gasparyan Armen Yuri,Ayvazyan Lilit,Yessirkepov Marlen,Kitas George D
Expert opinion on drug metabolism & toxicology
INTRODUCTION:Colchicine has been successfully used for the treatment of neutrophilic disorders such as familial Mediterranean fever (FMF), Behçet disease (BD) and gout. There is a growing interest in its cardiovascular effects. AREAS COVERED:A MEDLINE/PubMed search for English articles published from January 1972 to June 2015 was completed using the following terms: therapy, pharmacokinetics, efficiency, side effects, toxicity, heart, colchicine, inflammation, FMF, amyloidosis, BD, gout, cardiovascular disorders, pericarditis, arrhythmias, inflammation, neutrophils, platelets. EXPERT OPINION:By targeting neutrophils, endothelial cells and platelets, inhibiting mitosis, vascular hyperplasia and fibrosis, colchicine improves outcomes of pericarditis, myocardial ischemia and coronary interventions. Studies in neutrophilic rheumatic diseases and cardiovascular disorders demonstrated that oral colchicine at doses of 0.5 - 2.5 mg/daily is useful for treating pericarditis, myocardial ischemia and coronary occlusion. In rheumatic and cardiovascular disorders, therapeutic doses of the drug reduce C-reactive protein to levels below 2 mg/L, prevent myocardial damage and preserve normal values of atrial and ventricular impulse generation. One of the drug's frequent side effects is diarrhea, which is treated by diet modification or temporary discontinuation of the therapy. Certain drugs (macrolides, statins), comorbidities and certain genetic factors increase risk of colchicine toxicity.
10.1517/17425255.2015.1076391
Mean platelet volume and β-thromboglobulin levels in familial Mediterranean fever: effect of colchicine use?
Abanonu Gul Babacan,Daskin Alper,Akdogan Mehmet Fatih,Uyar Seyit,Demirtunc Refik
European journal of internal medicine
BACKGROUND:Many studies have shown that subclinical inflammation persisted during remission period of Familial Mediterranean Fever (FMF) patients but long term effects of subclinical inflammation in these patients aren't clearly known. Besides, a few of the recent studies revealed that risk of atherosclerosis had increased in FMF patients. β-Thromboglobulin (β-TG) is considered as a sensitive marker of platelet activation. In this study Mean Platelet Volume (MPV) and β-TG levels were evaluated in FMF patients. METHODS:Following the Local Ethics Committee's consent, 25 FMF patients were included in the study. Twenty eight age and sex matched healthy volunteers were recruited as a control group. Lipid profile, inflammatory parameters, hemogram, β-TG, MPV were assessed. Statistical analysis was performed with SPSS for Windows 16.00. RESULTS:Group I consisted of 25 FMF cases (16 females, 9 males; mean age: 35.72 ± 12.34 years), Group II consisted of 28 cases (22 females, 6 males; mean age 31.78 ± 10.31 years). There was no statistically significant difference between the groups in terms of age and gender distribution, smoking status, total cholesterol, triglyceride, LDL and MPV (p>0.05). HDL levels were found to be statistically lower in Group I (p:0.04). Median β-TG levels was significantly higher in Group II than Group I (129.50 (range:372.00) ng/mL versus 104.00 (range:212.80) ng/mL respectively; p:0.03). CONCLUSION:In this study MPV and β-TG were evaluated for FMF cases and healthy controls, β-TG levels were found significantly lower among patients; we hypothesized that this difference may have resulted from the effect of colchicine use on platelet functions.
10.1016/j.ejim.2012.04.007
Effects of colchicine treatment on mean platelet volume and the inflammatory markers in recurrent aphthous stomatitis.
Seçkin Havva Yıldız,Bütün Ilknur,Baş Yalçın,Takcı Zennure,Kalkan Göknur
The Journal of dermatological treatment
OBJECTIVE:Recurrent aphthous stomatitis (RAS) is the most commonly seen inflammatory disease in the oral mucosa affecting 5%-25% of the general population. The etiology of RAS is still not fully understood and its treatment is very challenging. With its anti-inflammatory affects, colchicine is used for systematic treatment of RAS. In this study, we want to examine the effects of colchicine on platelet density, mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and red cell distribution width (RDW) of the patients with RAS. METHODS:Fifteen male and 45 female RAS patients that were taking colchicine were investigated retrospectively. The whole blood parameters of the patients were observed before starting colchicine treatment and in the third month of colchicine treatment. RESULTS:Significant decrease in the levels of NLR, white blood cell count and RDW of the RAS patients under colchicine treatment was observed. Moreover, no changes were seen on MPVs, PLRs and hemoglobin (Hb) levels. CONCLUSION:It was determined that colchicine lowers the levels of NLR, white blood cell count and RDW. Furthermore, no changes were seen on MPVs, PLRs and Hb levels.
10.3109/09546634.2015.1116680
Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects.
Inflammation
The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.
10.1007/s10753-015-0237-7
Procoagulant Effects of Low-Level Platelet Activation and Its Inhibition by Colchicine.
Reddel Caroline J,Pennings Gabrielle J,Curnow Jennifer L,Chen Vivien M,Kritharides Leonard
Thrombosis and haemostasis
Platelets play an important role in diseases such as cardiovascular disease and cancer, especially through their release of extracellular vesicles (EVs) and role in thrombosis. The effects of the anti-inflammatory drug colchicine on platelets are not well understood. We investigated the effect of colchicine on the release of pro-coagulant EVs from platelets under low-level activation. Citrated platelet-rich plasma (PRP) from healthy donors was incubated with 2 mM colchicine or vehicle at 37°C for 30 minutes with gentle rotation. The incubation conditions caused mild platelet activation (expression of CD62P and increased surface lactadherin binding) and release of EVs expressing phosphatidylserine (PS, measured by binding of lactadherin), CD61 and CD62P, both of which were attenuated by colchicine. The incubation conditions shortened the delay to fibrin generation and this correlated with elevated levels of PS+/CD61+ EVs. Removal of EVs from plasma abrogated clot formation in the overall haemostatic potential (OHP) assay. Colchicine decreased levels of both PS+/CD61+ and CD62P+ EVs and abrogated the shortened delay to fibrin generation achieved by platelet activation. Similar results were observed after incubation of PRP with 200 µM vinblastine, suggesting a microtubular effect. An alternative method of platelet activation using platelet agonists 20 µM ADP or 10 µM epinephrine also increased CD62P+ EV levels, and this too was attenuated by prior incubation with colchicine. Our novel findings demonstrate procoagulant effects of low-level platelet activation and EV formation which are inhibited by colchicine.
10.1055/s-0038-1636915
Colchicine reduces platelet aggregation by modulating cytoskeleton rearrangement via inhibition of cofilin and LIM domain kinase 1.
Cimmino Giovanni,Tarallo Roberta,Conte Stefano,Morello Andrea,Pellegrino Grazia,Loffredo Francesco S,Calì Gaetano,De Luca Nicola,Golino Paolo,Trimarco Bruno,Cirillo Plinio
Vascular pharmacology
INTRODUCTION:Platelets activation/aggregation with subsequent thrombus formation is the main event in the pathophysiology of acute coronary syndrome. Once activated, platelets show an extensive cytoskeleton rearrangement that leads to recruitment of additional platelets to finally cause haemostatic plug formation. Thus, the cytoskeleton plays a pivotal role in this phenomenon. Colchicine (COLC) is an anti-inflammatory drug proven to reduce major cardiovascular events in patients with coronary artery disease. The molecular mechanisms by which COLC exerts these protective effects remain partially still unknown. Since COLC causes disruption of tubulin, a component of cell cytoskeleton, we investigated whether this drug might interfere with platelet aggregation by acting on cytoskeleton rearrangement. METHODS AND RESULTS:Platelets isolated from healthy volunteers were activated with Adenosine Diphosphate (ADP, 20 μM) Collagen (COLL, 60 μg/ml) and Thrombin Activating Receptor Peptide (TRAP 25 μM) with/without COLC 10 μM pretreatment. After stimulus, aggregation was measured by light aggregometry overtime. Microtubules structure was assessed by immunohistochemistry and key proteins involved in regulation of actin-filament assembly and contractility such as Myosin Phosphatase Targeting subunit (MYPT), LIM domain kinase 1(LIMK1) and cofilin were evaluated by Western Blot analysis. Colchicine pretreatment significantly blunted ADP/COLL/TRAP-induced platelet aggregation (up to 40%). COLC effects appeared mediated by microtubules depolymerization and cytoskeleton disarrangement associated to inactivation of MYPT and LIMK1 that finally interfered with cofilin activity. CONCLUSIONS:Our data indicate that colchicine exerts anti-platelet effects in vitro via inhibition of key proteins involved in cytoskeleton rearrangement, suggesting that its beneficial cardiovascular properties may be due, at least in part, to an inhibitory effect of platelet activity.
10.1016/j.vph.2018.09.004