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PubMed1982

Effect of colchicine on the uptake of prolactin and insulin into Golgi fractions of rat liver.

In previous studies we have shown that 125I-labeled prolactin is taken up by a receptor-dependent process and concentrated in an intact form in Golgi elements from female rat liver (J. Biol. Chem., 1979, 254:209-214). In this study we have examined the effect of colchicine on this uptake process into Golgi elements. Colchicine [25 mumol (10 mg)/100 gm body wt] was injected intraperitoneally in adult female rats, and hepatic Golgi fractions were prepared at 1, 2, and 3 h postinjection. The enzyme recoveries and morphological appearance of fractions from colchicine-treated and control (alcohol alone) animals were similar. At times greater than 1 h after colchicine there was a marked (greater than 60%) inhibition of uptake of 125I-ovine prolactin (125I-oPRL) into Golgi light and intermediate fractions but no inhibition of uptake into Golgi heavy and plasmalemma elements. At times from 2 to 45 min postinjection, 125I-oPRL was extracted from Golgi elements and found to be largely intact as judged by rebinding to receptors. The inhibitory effect of colchicine was seen at doses ranging from 0.25 mumol to 25 mumol/100 g body wt. Vincristine also inhibited 125I-oPRL uptake into the Golgi light and intermediate fractions but lumicolchicine had no inhibitory effect. There was a smaller effect of colchicine both at early (1 h) and later (3 h) times on the extent and pattern of 125I-insulin uptake. Colchicine treatment did not produce a significant change in lactogen receptor levels in the Golgi fractions. These results demonstrate that colchicine treatment inhibited the transfer of prolactin into Golgi vesicular elements. The much smaller effect on insulin uptake suggests that there may be differences in the manner in which the two hormones are handled in the course of internalization.

Animals↗

PubMed1974

Blockage of amyloid induction by colchicine in an animal model.

Colchicine was found to have a strong inhibitory effect on amyloid induction in an animal model. When CBA/J mice were treated with colchicine concurrently with the amyloid induction regimen, the incidence of amyloidosis was, depending upon the dosage of colchicine, significantly decreased (0.005-0.010 mg colchicine per day) or completely blocked (more than 0.015 mg colchicine per day). The colchicine treatment was effective not only when colchicine was given for the entire course of the amyloid induction regimen but also when it was given only in the late pre-amyloid or the amyloid phase of the regimen or to the recipients after the transfer of amyloid. The data suggest the colchicine is effective in blocking amyloidogenesis at its final stage(s), while it may not affect significantly amyloid already deposited in the tissue.

Amyloid↗

PubMed1999

Colchicine inhibits isoflurane-induced preconditioning.

BACKGROUND: When administered before prolonged myocardial ischemia and reperfusion, isoflurane exerts potent cardioprotective effects similar to those inferred by ischemic preconditioning. To determine whether an intact cytoskeleton is critically important in isoflurane-induced preconditioning, the authors used a rabbit model in which isoflurane-induced myocardial preconditioning decreases myocardial infarct size (IS) substantially. In this model, the authors tested whether the microtubule depolymerizing agent, colchicine, would inhibit isoflurane-induced myocardial preconditioning. METHODS: Myocardial IS was measured in four groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed only in the pretreatments given, and only the control group received no pretreatment. An isoflurane-preconditioned group was pretreated with 15 min of end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-colchicine group was administered 2 mg/kg colchicine intravenously before isoflurane pretreatment. A colchicine-control group was administered 2 mg/kg colchicine but no isoflurane pretreatment. Myocardial IS and area at risk (AR) were defined by staining. Data were analyzed by analysis of variance or covariance. RESULTS: Infarct size, expressed as a percentage of AR (IS:AR) was 33.6%+/-8.8% (SD) in the control group. Isoflurane preexposure reduced myocardial IS:AR significantly, to 11.8%+/-9.1%. Colchicine pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 32.6%+/-8.7%). Colchicine alone did not alter IS (IS:AR = 27.6%+/-7.1%; P = not significant). CONCLUSIONS: Colchicine abolished the preconditioning effect of isoflurane but did not increase IS when administered alone. An intact microtubular cytoskeleton is critically important in the process of volatile anesthetic-induced preconditioning.

Anesthetics, Inhalation↗

PubMed1995

Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced pancreatitis in comparison with the microtubule stabilizer taxol.

Effects of colchicine, a microtubule-disrupting agent, on rate exocrine pancreas were examined in comparison with the microtubule stabilizer Taxol for the purpose of analyzing the pathogenesis of cerulein-induced acute pancreatitis. Taxol ameliorated the inhibition of pancreatic secretion, elevation of serum amylase level, pancreatic edema, and histological alterations induced by supramaximal cerulein stimulation. In contrast, colchicine by itself and colchicine followed by cerulein stimulation (maximal and supramaximal) inhibited pancreatic secretion but did not induce the hyperamylasemia, pancreatic edema, or formation of large vacuoles, which characterized cerulein-induced pancreatitis. Electron microscopic studies in the colchicine-treated rats revealed that transport vesicles were accumulated in the supranuclear region and that no large vacuoles were observed in the apical lesion. Immunofluorescence studies confirmed that colchicine inhibited pancreatic secretion and disrupted the arrangement of microtubules. Posttreatment of colchicine did not prevent the development of cerulein-induced pancreatitis. Vinblastine, another microtubule-disrupting drug, as well as colchicine, inhibited pancreatic secretion but did not induce acute pancreatitis. The results obtained in this study suggest that microtubule disorganization at a specific step in the process of intracellular vesicular transport causes cerulein-induced pancreatitis and that this step is more apical than that at which colchicine inhibits secretion in the pancreatic acinar cell.

Acute Disease↗

PubMed2002

Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial.

BACKGROUND: Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis. OBJECTIVE: This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis. METHODS: Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo. MAIN OUTCOME MEASURES: Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety. RESULTS: Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference. CONCLUSIONS: Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis.

Adolescent↗

PubMed1984

Colchicine-induced alteration of hormone-stimulated cyclic AMP synthesis in pig skin (epidermis).

Effects of colchicine on the epidermal adenylate cyclase systems were investigated. When pig skin (epidermis) was incubated in RPMI 1640 medium without the addition of serum, the beta-adrenergic adenylate cyclase response (epinephrine-induced cyclic AMP accumulations) gradually decreased, whereas adenosine and histamine responses remained high or increased during the long-term (up to 48 h) incubation period. The addition of colchicine (1 mumol/liter) in the incubation medium resulted in an increase in the beta-adrenergic responsiveness and a decrease in adenosine and histamine responsivenesses. The effects of colchicine were both time- and concentration-dependent; they could be observed after 9-12 h incubation, and the maximal effect was obtained at a concentration of 0.1 mumol/liter. Similar effects were observed by the addition of another microtubule-disruptive agent, vinblastine. On the other hand, cytochalasin B, which affects the microfilament system, apparently decreased the beta-adrenergic response and increased adenosine and histamine responses during the long-term incubation period. The addition of serum in the incubation medium resulted in essentially the same effect as that of colchicine; in the presence of serum, colchicine-treated skin responded much more markedly to epinephrine (and much less to adenosine and histamine) than the control skin after 24- and 48-h incubation. Previously we reported that hydrocortisone has similar potentiating effects on the beta-adrenergic system of epidermis. The comparison of the effects of both compounds revealed that colchicine had a stronger effect than hydrocortisone, and furthermore, the simultaneous addition of both compounds (colchicine and hydrocortisone) in the incubation medium resulted in the more marked increase of beta-adrenergic response than the single addition of each chemical. Our overall results, coupled with the finding that hydrocortisone has no toxic effects on the adenosine- or histamine-adenylate cyclase system of epidermis, suggest that colchicine affects epidermal adenylate cyclase systems probably through a mechanism that is independent of glucocorticoid (hydrocortisone) effect.

Adenosine↗

PubMed1982

Colchicine-induced modulation of collagenase in human skin fibroblast cultures. II. A probe for defective regulation in epidermolysis bullosa.

The addition of colchicine to cultures of normal human skin fibroblasts produces a significant stimulation of collagenase. Because this finding implies a role for the microtubule system in the regulation of normal collagenase synthesis, we have used colchicine as a probe for aberrations in this enzyme in epidermolysis bullosa. In fibroblast cultures from the dominant simplex, dominant dystrophic, and recessive letalis forms of epidermolysis bullosa, 10(-6) M colchicine produced approximately a 2-fold increase in collagenase in the culture medium, a finding shown by biosynthetic studies to be attributable to enhanced synthesis of enzyme protein. In the case of typical recessive dystrophic epidermolysis bullosa, a disease characterized by excessive collagenase synthesis, the fibroblasts could also be stimulated to produce additional collagenase, despite having elevated baseline synthetic rates. In contrast, fibroblasts isolated from one recessive epidermolysis bullosa patient were resistant to the stimulatory effects of colchicine in concentrations up to 5 x 10(-6) M. In the absence of colchicine, collagenase synthesis in this patient's cells (termed REBc-) was 3-4 times that of normal controls, suggesting that the as yet undefined cellular function that is abrogated (or stimulated) by colchicine in normal cells may have been genetically impaired in these REBc- cells. Despite the resistance to colchicine, as manifested by the failure to stimulate collagenase, gross parameters of microtubular function, such as cell replication, were intact. Phenotypically, this patient had a form of epidermolysis bullosa intermediate between typical recessive dystrophic and recessive letalis forms of the disease. Although an experimentally induced blister was located in the lamina lucida, hypoplastic anchoring fibrils were also observed. These findings, in addition to the marked increase in collagenase synthesis, suggest the possibility that this patient may represent a compound heterozygote of two forms of epidermolysis bullosa and that colchicine may be useful in defining other such patients.

Cells, Cultured↗

PubMed1994

Colchicine concentration in leukocytes of patients with familial Mediterranean fever.

Free and total plasma, granulocyte and mononuclear cell colchicine concentrations were measured by radioimmunoassay in 30 patients with familial Mediterranean fever treated with colchicine 0.5 to 2 mg day-1. Colchicine concentrations showed a large intersubject variability in plasma (0.13-1.75 ng ml-1), granulocytes (4 to 64 ng/10(9) cells), and mononuclear cells (11.4 to 57.6 ng/10(9) cells). Whereas unbound and total plasma colchicine concentrations were well correlated, no correlation was found between total or free plasma and granulocyte or mononuclear cell colchicine concentrations and dose of administered colchicine. In contrast, total or free plasma and granulocyte or mononuclear cell colchicine concentrations were correlated using a hyperbolic function indicating saturable colchicine distribution in both leukocyte populations.

Administration, Oral↗

PubMed2003

Efficacy of colchicine in patients with primary biliary cirrhosis poorly responsive to ursodiol and methotrexate.

OBJECTIVE: Approximately 20-30% of patients with primary biliary cirrhosis (PBC) respond fully to treatment with ursodeoxycholic acid (UDCA). The rest have progressive disease and eventually develop cirrhosis and liver failure. More effective treatment is needed. Methotrexate improved biochemical tests of liver function and liver histology in patients with PBC who had failed to respond to UDCA in one report and induced sustained biochemical and histological remission in another. The role of colchicine in PBC is unclear. We describe three patients with symptomatic PBC who responded very well to the addition of colchicine after they had failed to respond to UDCA alone and in combination with methotrexate. We suggest that colchicine should be tried in PBC patients who clearly fail to respond to UDCA. METHODS: Three patients with symptomatic biopsy-proven, antimitochondrial antibody-positive PBC failed to respond to UDCA and then to the addition of methotrexate. Colchicine was eventually added to the regimen. Symptoms, biochemical tests of liver function, and percutaneous liver biopsies were done at baseline, after treatment with UDCA, UDCA plus methotrexate, and UDCA plus methotrexate plus colchicine. RESULTS: All three patients responded after colchicine was added to UDCA and methotrexate. Symptoms, biochemical tests of liver function, and liver histology improved in all, and blood tests normalized in two. CONCLUSIONS: Colchicine may be effective treatment in some symptomatic patients with PBC who respond incompletely to UDCA alone or in combination with methotrexate. Colchicine may be tried in such patients.

Adult↗

PubMed2003

Treatment of chronic constipation with colchicine: randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Refractory constipation is a common GI complaint seen by physicians in all practice settings. We have previously shown that p.d. colchicine (0.6 mg t.i.d.) increases the number of spontaneous bowel movements, hastens GI transit, and improves GI symptoms in patients with chronic constipation during an 8-wk, open-label therapeutic trial. The aim of this study was to determine if p.d. colchicine will increase spontaneous bowel movements and accelerate colonic transit in patients with idiopathic chronic constipation in a randomized, placebo-controlled, crossover trial. METHODS: A total of 16 patients (15 women, one man) with a mean age of 47 yr (age range 25-89) with chronic idiopathic constipation who were refractory to standard medical therapy participated in the study. Patients randomly received either colchicine 0.6 mg p.o. t.i.d. or an identical placebo p.o. t.i.d. for a total of 4 wk in a double-blind, crossover fashion. Patients recorded their daily number of bowel movements and daily symptoms of daily nausea, abdominal pain, and bloating. Mean colonic transit was calculated at baseline, weeks 6 and 12. RESULTS: Colchicine increased the number of bowel movements and accelerated colonic transit compared with baseline and placebo conditions. There were no significant differences between conditions on ratings of nausea and bloating. During colchicine administration, mean abdominal pain was greater than the baseline or placebo conditions, however, the pain decreased significantly by the last week the patient was on colchicine. CONCLUSION: Colchicine increases the frequency of bowel movements and hastens colonic transit in patients with chronic constipation. Colchicine may be an effective agent available to practitioners to treat a subset of patients with chronic constipation who are refractory to standard medical therapy.

Adult↗

PubMed1978

Effect of colchicine on drug absorption from the rat small intestine in situ and in vitro.

The effect of colchicine (1 mg/kg intraperitoneally on two successive days) on the absorption of isoniazid, quinidine and sulphafurazole (sulfisoxazole) from the rat small intestine was studied in situ and in vitro. Colchicine produced two different types of histological damage in the small intestine, one with degenerative and the other with regenerative changes predominating. The small intestinal surface area was variably reduced. The colchicine-treated rats were lethargic and hypothermic as compared to controls. Colchicine retarded the disappearance of fluid and all three drugs from the small intestinal lumen in situ 2 days after the first colchicine injection. In vitro the total amounts of fluid and drugs passed through the intestinal wall were not significantly changed by colchicine, although there was a slight tendency towards an increased absorption of quinidine. Hence, colchicine as an antimitotic drug decreases drug absorption from the rat small intestine in situ, apparently due to the decreased surface area of the small intestine, the decreased water flux through the intestinal wall, the retarded intestinal motility and hypothermia of the rats. In vitro the changes are small, which makes the in vitro tests less suitable for studying the effect of colchicine on absorption.

Animals↗

PubMed1977

The effects of nerve section and of colchicine treatment on the density of mechanosensory nerve endings in salamander skin.

We have shown that when one of the spinal nerves supplying the salamander hind limb is cut or treated with colchicine, the fields of the remaining nerves enlarge in area; whereas nerve section produces Wallerian degeneration, the colchicine-treated nerves conducted action potentials normally and their peripheral fields remained unchanged in area (Aguilar, Bisby, Cooper & Diamond, 1973). Since colchicine-treatment reduced neuronal transport, and nerve-section eliminated it, we proposed that nerve sprouting is regulated by factors normally conveyed to the endings by axoplasmic transport. 1. We have now investigated the effects of colchicine on the thresholds and distribution of individual mechanosensory endings in the skin. If reduction of neuronal transport were enough to cause the threshold to be increased to the point of total unresponsiveness, then this could be a sign of an early stage of degernation in those terminals. It could then be hypothesized that products of degeneration were providing a stimulus for adjacent nerves to sprout. 2. Quantitative physiological studies of the effects of colchicine doses known to interfere with fast axoplasmic transport, indicate that in some experiments the terminal field of the treated nerve was invaded by sprouting fibres from neighbouring axons, when its own endings were unchanged in number, distribution and sensory thresholds. In other experiments the colchicine-treated nerve endings showed an increase in threshold but their function was otherwise unchanged; a similar adjacent nerve sprouting occurred. In a final group, colchicine caused total unresponsiveness of some endings of the treated nerve. 3. When a region of skin was partially denervated by nerve section, the physiological analysis indicated that the number of new mechanosensory endings which sprouted from the remaining axons exactly matched the number lost by nerve degeneration: furthermore the distribution of the endings was normal. It therefore appears that sprouting ceased when the original density of mechanosensory endings in the skin was restored. 4. The possibility that the drug induced sprouting as a consequense of a direct action on the skin is unlikely. With [3H]colchicine, we found that the accumulation of label in the skin of the untreated limb, in which sprouting did not occur, equalled that of the opposite limb. 5. The present results lend support to the original hypothesis of Aguilar et al. (1973), which proposed that collateral sprouting of intact nerves occurs when the supply of neuronally transported factors becomes inadequate to balance out the effects of a postulated target-tissue stimulus. In the Discussion other examples of collateral nerve sprouting, such as that following adjacent denervation, are shown to be explainable by this hypothesis.

Action Potentials↗

PubMed1979

Microtubules, colchicine, and lymphocyte blastogenesis.

We have studied the time course of disassembly of microtubules of resting and stimulated mouse lymphocytes caused by the drug colchicine, as well as the effect of this compound on DNA and RNA synthesis of human and mouse lymphocytes. Fine-structure studies with the electron microscope showed a great increase in number of microtubules resulting from stimulation of mouse lymphocytes by the mitogenic lectin Con A. The presence of a network of microtubules was demonstrated in resting lymphocytes by use of the technique of immunofluorescence; this technique was not effective for the study of the microtubules of stimulated lymphocytes in the blast stage. The disappearance of microtubular networks in some cells (approximately 25%) was caused by the protocol of colchicine treatment used in many laboratories (30 min at 10(6) M); a 6- to 8-h treatment was required to cause all cells to lose their microtubules. It is indicated in these findings that there is need for extreme caution in implicating microtubule disruption as the cause of certain colchicine effects, such as that on the Con A-induced inhibition of receptor-ligand migration. The addition of colchicine to stimulated cells at varying times of culture caused marked inhibition of DNA synthesis provided that sufficient time (approximately 20 h for maximum inhibition) elapsed between addition of the drug to the stimulated culture and assay of DNA synthesis. Our data on the time course of inhibition of DNA synthesis by alpha-methyl mannoside (alpha MM) and by colchicine do not exclude the possibility that the latter compound may act partially by affecting the commitment of stimulated lymphocytes to DNA synthesis but they show that it can inhibit well after commitment is complete. The later the time of assay of thymidine incorporation, the more disparate were the curves relating the effects of alpha MM and colchicine to DNA synthesis of human cells. In the case of mouse splenic lymphocytes, there was no resemblance between the time course of the alpha MM and of the colchicine effects. Synthesis of RNA after 12 h of culture of stimulated human lymphocytes was also sensitive to colchicine.

Animals↗

PubMed1981

Inhibition of microtubule polymerization by the tubulin-colchicine complex: inhibition of spontaneous assembly.

The inhibition of microtubule polymerization by colchicine requires the formation of tubulin-colchicine complexes, and inhibition of polymerization is proportional to the concentration of tubulin-colchicine complexes rather than to the total concentration of colchicine. Because the formation of such complexes is slow relative to polymerization, the kinetics of complex formation obscure the kinetics of inhibition of polymerization. We have taken defined quantities of preformed tubulin-colchicine complexes, relying on their slow dissociation, and added these to microtubule protein, which was allowed to polymerize by temperature shift to 37 degrees C. The degree of polymerization was then determined by measurement of turbidity at 400 nm. An appropriate kinetic analysis allowed us to distinguish effects of inhibitor on initiation and elongation phase of polymerization, without resorting to the use of initiation inhibitors. The results are consistent with a reversible association of tubulin-colchicine complex with microtubule ends blocking further elongation (K1 = 0.16 micro M). Steady-state measurements suggest that copolymerization of tubulin-colchicine complex is a minor factor under the conditions used. By contrast, little inhibition of initiation was observed, possibly because tubulin-colchicine complex competes with the tubulin dimer, but not with the larger oligomers required for the initiation process.

Animals↗

PubMed1988

Inhibition by colchicine of phospholipid secretion induced by lung distension.

The effect of colchicine, a microtubule disruptor, on phospholipid secretion stimulated by distension of fetal rabbit lungs was investigated. After colchicine injection and breathing for 45 min, pups were killed and their lungs were lavaged with colchicine. Controls were injected and lavaged with saline. All lungs were given static air inflation and a final lavage, and the returns were analyzed for phospholipid DNA, and lactate dehydrogenase. The first lavage after breathing yielded 33% less phospholipid with colchicine, 3.83 compared with 5.72 mg/g dry lung wt (P less than 0.05). The postinflation phospholipid yield was also significantly reduced with colchicine from 1.04 to 0.70 mg/g dry lung wt (P less than 0.05). The postinflation DNA was significantly reduced with colchicine, from 1.26 to 0.44 micrograms (P less than 0.01), suggesting reduced alveolar macrophages. Colchicine did not change the recovery by lavage of exogenous radioactive phospholipid. As reflected by ATP and lactate levels, tissue metabolism was well maintained. The results are interpreted to mean that colchicine reduced simultaneously lavage-associated phospholipid secretion, inflation-produced phospholipid secretion, and macrophage migration.

Adenosine Triphosphate↗

PubMed1979

Mechanism of action of colchicine in acute urate crystal-induced arthritis.

Phagocytosis of urate crystals by human or rabbit neutrophils induces the synthesis and release of a glycoprotein, the crystal-induced chemotactic factor (CCF), which is chemotactically active both in vitro and in vivo. It has been proposed that CCF is a prime mediator of the acute gouty attack. Colchicine has been shown to decrease the production and release of this factor in vitro. In these studies, colchicine, at nonleukopenic doses, is shown to abrogate the acute arthritis induced by monosodium urate crystals in rabbits, but to have no effect upon the arthritis induced by the injection of the purified cell-derived chemotactic factor. Serum colchicine levels were 0.48-0.58 muM at 30 min and 0.12-0.3 muM at 90 min after intravenous injection of 0.2 mg/kg colchicine. Peripheral blood polymorphonuclear leukocytes obtained from colchicine-treated animals migrated normally towards a chemotactic stimulus but failed to produce CCF after phagocytosis of monosodium urate crystals. The dialyzed synovial fluid from rabbits injected with microcrystalline sodium urate contained chemotactic activity that was not present when animals were also given intravenous colchicine or injected intra-articularly with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Furthermore, the synovial fluid from rabbits injected with microcrystalline sodium urate significantly decreased (125)I-CCF binding to neutrophils. The binding of (125)I-CCF to its neutrophil receptor was not significantly reduced by the synovial fluid of colchicine-treated rabbits nor by the synovial fluid of control rabbits injected with the chemotactic factor formyl-methionyl-leucyl-phenylalanine. Colchicine (10 and 0.1 muM) was shown to have no effect upon the binding of (125)I-CCF to its cell receptor.

Animals↗

PubMed1992

Toxicokinetics of colchicine in humans: analysis of tissue, plasma and urine data in ten cases.

1. A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2. Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 13 l h-1 and three-fold less than total body clearance (39 l h-1). The apparent volume of distribution was 21 l kg-1. 3. Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g-1); it was also found in the brain (125 ng g-1). 4. This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occurring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

Adolescent↗

PubMed2001

The inhibitory effects of colchicine on cell proliferation and mineralisation in culture.

Colchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of (3H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red. Our findings indicate that concentrations of colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the capacity to inhibit selectively bone-like cell mineralisation in culture, without affecting cell proliferation. Further clinical and laboratory studies are necessary to evaluate the effects of colchicine on biological processes involving the proliferation of osteoblasts and tissue mineralisation in vivo, such as the healing of fractures, the formation of heterotopic bone and neoplastic bone growth.

Animals↗