Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Colchicine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,207 records · Page 67Linked to original sources
PubMed1989

Effect of colchicine and vincristine on DNA synthesis in regenerating rat liver.

The increases in the activities of hepatic thymidylate synthetase and thymidine kinase were significantly suppressed at 24 h after 70% partial hepatectomy in rats which had been administered a microtubule disrupter, colchicine or vincristine. The decrease of these enzymic activities was accompanied by a reduction of DNA content in 24 h regenerating liver. The immunoblotting assay showed that the depression of the thymidylate synthetase activity by the injection of colchicine or vincristine was due to the decrease of the enzyme protein. These results indicate that colchicine and vincristine inhibit the DNA synthesis during liver regeneration by inhibiting the induction of the key enzyme in DNA synthesis.

Animals↗
PubMed1989

Colchicine prevents D-galactosamine-induced hepatitis.

The hepatoprotective effect of colchicine in a model of liver intoxication with galactosamine (GalN), 375 mg/kg, i.p., was studied in rats. At 0.5, 1, 3, 6, 18 and 24 h after GalN intoxication the following markers of liver damage were measured: serum activity of alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, hepatic calcium and glycogen contents, liver lipoperoxidation, and liver plasma membrane activity of alkaline phosphatase, gamma-glutamyltranspeptidase and high-affinity Ca2+-ATPase. 24 h after GalN intoxication increases in serum levels of alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase were observed along with decreases in plasma membrane activities of alkaline phosphatase, gamma-glutamyltranspeptidase, and high-affinity Ca2+-ATPase. A sharp increase of lipoperoxidative processes measured as malondialdehyde production was also observed. Pretreatment of rats with colchicine 10 micrograms/rat/day p.o. for 7 days before GalN injection prevented partially the toxic effects of GalN. When a dose of 50 micrograms/rat/day for 7 days was given the drug prevented almost completely the damage induced by galactosamine, with the exception of glycogen and serum alkaline phosphatase that remained different from controls. Time-course experiments showed that malondialdehyde formation increased 30 min after intoxication while all other changes became apparent from 6 h after treatment, suggesting that lipoperoxidation may be a prerequisite for galactosamine-induced damage. The protection offered by colchicine was related to its capacity to inhibit lipoperoxidation. Histochemical findings paralleled the biochemical results. The possible role of lipoperoxidation in galactosamine-induced liver damage is discussed.

Alanine Transaminase↗
PubMed1992

Expression of GAL mRNA in rat hypothalamus: effect of frontal deafferentation and colchicine treatment.

The expression of galanin (GAL) mRNA was determined by in situ hybridization after frontal deafferentation and colchicine treatment in the rat hypothalamus. Frontal deafferentation significantly increased the signal in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and dorsomedial nucleus (DMN). Colchicine treatment induced a diffuse enhancement of GAL mRNA in hypothalamic nuclei. When the two treatments were combined there was an additivity of GAL mRNA expression in the previous hypothalamic nuclei and also in the arcuate nucleus (AN), where the single treatments did not modify the signal. These results suggest the regulation of GAL mRNA expression mediated by a multineuronal pathway, separate from the colchicine-induced GAL mRNA increase.

Afferent Pathways↗
PubMed1986

Lipoxygenase inhibitor and colchicine as anti-arthritic agents in the rat.

The non-steroidal anti-inflammatory agents do not have identical activities on the various pathways of arachidonic acid metabolism. The purpose of this study is to examine and compare the activities of colchicine, an anti-arthritic agent, indomethacin, a known prostaglandin synthesis inhibitor and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, in an experimental model of arthritis. Acute arthritis of the knee was induced in rats by injection of lipopolysaccharide (LPS) into the joints. Arthritis was characterized by an increase in joint diameter (18%), increased synovial weight (34%) and an increase in synovial prostaglandin E (PGE) production (56%). While administration of all of the agents examined abolished LPS-induced joint diameter and synovial weight increase, only indomethacin reduced increased PGE content. NDGA and colchicine had no inhibitory effect on LPS-induced PGE production, and moreover they actually stimulated PGE production when compared to control values. It is concluded that: Among the mediators of the inflammatory process are factors sensitive to colchicine and NDGA which are not PGs. Lipoxygenase products of arachidonic acid including leukotrienes may have an important role in inflammation. Leukotrienes and prostaglandins may act in concert in mediating the inflammatory process.

Animals↗
PubMed1991

Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism.

Vinblastine or colchicine, administered intraperitoneally to B6D2F1 mice with advanced subcutaneous colon 38 tumours, induced substantial tumour growth delays with progressive development of haemorrhagic necrosis beginning within 8 hours of treatment. Two multidrug-resistant P388 leukaemia sublines, refractory to vinblastine and vincristine when grown as intraperitoneal ascites, were sensitive to necrosis induction when grown as subcutaneous tumours. Vascular labelling with two fluorescent markers indicated that vincristine substantially reduced tumour blood flow within 4 hours after treatment. The effects of vinblastine, vincristine and colchicine were similar to those of tumour necrosis factor alpha in that: (a) similar tumour necrosis and blood flow changes were induced, (b) coadministration of the serotonin antagonist cyproheptidine prevented tumour necrosis and (c) plasma nitrate levels were elevated, indicative of the stimulation of oxidation of L-arginine to nitric oxide. The results suggest that vinca alkaloids and colchicine act on solid tumours by host cell-mediated vascular effects as well as by direct tubulin-mediated cytotoxicity.

Adenocarcinoma↗
PubMed1987

Effect of colchicine on some electrical properties of rat small intestine.

The effect of colchicine on the short circuit current (s.c.c.), potential difference (p.d.) and tissue resistance was investigated in vitro using rat jejunum. The electrogenic transfer of glucose, galactose, glycine and valine was also measured in the presence and absence of the drug. Colchicine (0.05 mM and 0.1 mM) caused a dose-dependent decrease in s.c.c. and p.d. in the presence of glucose but had no significant effect on the tissue resistance. Colchicine at (0.1 mM) increased the "apparent Km" of glucose (140% P less than 0.001) galactose (135% P less than 0.001) glycine (43% P less than 0.001) and valine (47% P less than 0.001) but had no significant effect on the p.d.max of these substrates.

Animals↗
PubMed1990

Microtubular response to colchicine in adult and fetal rat hepatocytes.

1. Colchicine and related anti-microtubular drugs impair plasma protein secretion from adult rat liver explants 2-3-fold more than from fetal tissue. 2. Indirect immunofluorescence microscopy of cultured adult and fetal hepatocytes demonstrated that hepatocytes of both ages contain large numbers of densely packed microtubules which are equally disassembled by 10 microM colchicine. 3. Colchicine (10 microM) reduced secretion of [14C]leucine-labelled proteins from cultured adult hepatocytes by about 50% but did not significantly impede fetal secretion. 4. These results confirmed that plasma protein secretion can proceed without an intact microtubular system in fetal hepatocytes.

Animals↗
PubMed1988

Direct neurotoxic effects of colchicine on cholinergic neurons in medial septum and striatum.

The mitotic/microtubule inhibitor, colchicine, is known to be neurotoxic to certain populations of neurons. We report here that a single intraventricular injection of colchicine exerts specific neurotoxic effects on cholinergic neurons while sparing GABAergic neurons in the medial septal nucleus and striatum. It is hypothesized that the colchicine-induced loss of choline acetyltransferase immunoreactive neurons represents degeneration of the cholinergic neurons as a result of disruption of the retrograde axoplasmic transport of a neurotrophic factor.

Animals↗
PubMed1991

Effects of colchicine on the development of tachyphylaxis to calcitonin gene-related peptide in the guinea pig heart.

Calcitonin gene-related peptide (CGRP) induced a concentration-dependent positive inotropic and chronotropic effect on the spontaneously beating right atrium subject to tachyphylaxis upon extended incubation. This stimulatory effect was mimicked by capsaicin. After incubation with colchicine there was a marked attenuation of the decline in the prolonged response to CGRP or capsaicin and no development of CGRP tachyphylaxis. Colchicine incubation did not influence the capsaicin-induced stimulation of the frequency or CGRP outflow in whole heart preparations. Thus, the present data suggest that the development of CGRP tachyphylaxis is a specific receptor-mediated event which can be inhibited by colchicine, probably by disruption of membrane bound proteins.

Animals↗
PubMed1981

Elevated sialyltransferase activity in the intestinal lymph of colchicine-treated rats.

There is a marked increase in sialyltransferase activity (EC 2.4.99.1) in serum and a profound change in the endogenous acceptor property of sialyltransferase in the intestine of colchicine treated rats (Fraser, Ratnam, Collins and Mookerjea, (1980) J. Biol. Chem. 255, 6617-6625). To ascertain the contribution of intestine as a source of this elevated serum enzyme, sialyltransferase and other enzymes activities were measured in intestinal lymph before and after colchicine treatment. There was a 4-fold increase of the enzyme activity in lymph 3 h after treatment. The lymph flow rate, protein concentration and composition as measured by polyacrylamide gel electrophoresis were not affected. The kinetic properties of lymph sialyltransferase (protein and time dependence, pH optima and Km values for the substrate CMP-sialic acid) were essentially unchanged after treatment and were similar to the serum sialyltransferase. Alkaline phosphatase and lactic dehydrogenase activities remained unchanged. Although intestinal lymph sialyltransferase was increased by colchicine, enterectomy did not prevent the rise of serum sialyltransferase suggesting that the intestine is not a major source of the serum enzyme.

Animals↗
PubMed1976

Effect of colchicine and vinblastine on crayfish neuromuscular junction.

1. The effect of the microtubule disrupting agents colchicine and vinblastine was studied on crayfish excitatory neuromuscular transmission. 2. Colchicine, in concentrations of 1-3 mM, brought about a decrease in the amplitudes of intracellularly recorded excitatory junctional potentials (ejps). Vinblastine, in concentrations of 0.08-0.32 mM, increased the amplitudes of ejps. 3. Drug-induced alterations in ejp amplitude resulted from changes in quantal content of the excitattory nerve as determined by extracellular recording. The effect could not be explained by changes in quantal size. 4. The effect of colchicine and vinblastine does not appear to be related to an action on microtubules.

Action Potentials↗
PubMed1990

In vivo prevention and reversal by the antimitotic colchicine and other related compounds of some porphyrinogenic drug action on heme pathway.

1. The effect of colchicine, vincristine and griseofulvin (GRIS) on the porphyrinogenic action of 2-allyl-2-isopropylacetamide (AIA) and veronal was studied in vivo and using the in vitro experimental model of tissue explant cultures. 2. Complete prevention by colchicine was found in liver and heart explant from animals treated with AIA and veronal. 3. Vincristine, GRIS and colchicine reversed AIA induction in liver explants, however reversal was partial or nil in skin and heart explants depending on the antimitotic and the tissue. 4. The usefulness of the combination of the in vivo experimental model and the in vitro explant tissue culture model, for this kind of studies is emphasized.

5-Aminolevulinate Synthetase↗
PubMed1991

Colchicine enhances mRNAs encoding the precursor of calcitonin gene-related peptide in brainstem motoneurons.

Hybridization signals indicating mRNAs encoding the precursor of calcitonin gene-related peptide (CGRP) and CGRP immunoreactivity were detected on parallel sections containing brainstem motor nuclei using in situ hybridization histochemistry and immunohistochemistry. In untreated and saline-injected rats the motoneurons in the hypoglossal, facial motor nuclei and in the ambiguus nucleus showed weak to moderate hybridization signals. In these motoneurons CGRP immunoreactivity was restricted to the Nissl bodies of the perikarya. Twenty-four and 42 hours after intracerebroventricular colchicine injection the intensity of both the hybridization signal and the immunoreaction product increased. The distribution of CGRP immunoreactivity changed from discrete perikaryal localization to diffuse reaction in the perikarya and along the proximal dendritic tree. Motoneurons in the rest of the brainstem motor nuclei (VIth, Vth, IVth and IIIrd) of untreated and saline-injected rats showed neither hybridization signal nor CGRP immunoreactivity. After intracerebroventricular injection of colchicine these motoneurons showed both hybridization signal and CGRP immunoreactivity. In all nuclei the size of motoneurons decreased and their Nissl structure changed to an amorphous basophilic mass following colchicine treatment.

Animals↗
PubMed1979

Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil.

Multiple sclerosis (MS) is a disease with no known treatment. In view of this and of its distressing nature patients are attracted by any new concepts. As a reaction to this neurologists are sometimes excessively sceptical and fail to consider new approaches seriously. Recent attempts have been made to treat multiple sclerosis with polyunsaturated fatty acids and with colchicine. This approach is not arbitrary and is firmly grounded in fundamental basic scientific concepts. In patients with multiple sclerosis there is evidence of both an abnormality in essential fatty acid metabolism and an abnormality in lymphocyte function. It is now apparent that the fatty acid abnormality may cause the lymphocyte abnormality and that both may be improved by dietary manipulation. There is also evidence that the demyelination may be associated with recurrent inflammatory episodes and with entry of calcium into the cytoplasm. In vitro colchicine has been shown to have actions compatible with regulation of cytoplasmic calcium and in two diseases characterised by intermittent inflammatory episodes (Behçets syndrome and familial Mediterranean fever) it has been found to prevent or to reduce the severity of such episodes. Preliminary results suggest that combined therapy with evening primrose oil and colchicine may be of considerable value.

Behcet Syndrome↗
PubMed1980

La crosse virus production and export have a colchicine-sensitive step.

In the present investigation, the effect of colchicine on La Crosse virus production and export was tested. Colchicine-treated, La Crosse virus-infected cells: (1) had decreased mean virus titers compared with those of control cells; (2) had a ratio of released to cell-associated virus of 1-1.9 whereas control cells had a ratio of 13. A colchicine-sensitive step, possibly involving microtubules, may be involved in virus production and/or release from the cell.

Animals↗
PubMed1991

Ultrastructural effects of colchicine on perikarya and initial segment of rat retinal ganglion cells.

Our ultrastructural study was focused on the perikaryal region and initial segment of the axon of rat retinal ganglion cells in controls and after intraocular injections of colchicine. In control rats that region contained, among other organelles, elements of the Golgi complex and, close to them, short isolated microtubules oriented preferentially toward the axon where they funnel and aggregate in bundles. One day after sufficient doses of colchicine to inhibit axoplasmic transport (2-20 micrograms) these cytoplasmic microtubules were absent, whereas some axonal microtubules were still present but reduced in number. In addition, colchicine induced an altered distribution of organelles, leaving empty spaces in the periphery and most organelles concentrated in the perinuclear region, especially around Golgi elements where numerous vesicles and tubules accumulate at the trans face of Golgi elements. These results suggest that the vesicles that leave the Golgi and have been directed towards axoplasmic transport may need the cytoplasmic microtubules located between Golgi elements and the axonal initial segments to reach the axon.

Animals↗
PubMed1985

Enhanced acetylcholinesterase staining in hippocampal area CA3 after lesion of granule cells by infusion of colchicine.

Unilateral infusion of colchicine into the lateral ventricle produced relatively selective destruction of dentate granule cells in the ipsilateral dorsal hippocampal formation of the rat. Timms silver sulfide stain is markedly reduced in the mossy fiber layer on the colchicine treated side but is normal contralaterally. After colchicine treatment, an increase in acetylcholinesterase staining is apparent in the apical dendritic zone of CA3 pyramidal cells. This enhanced staining is localized in the proximal apical dendritic layer of CA3, a region normally occupied by the mossy fiber terminals of dentate granule cells. These results suggest that cholinergic fibers proliferate in CA3 after granule cell lesion and may participate in reinnervation of the denervated area.

Acetylcholinesterase↗
PubMed1991

Compensatory alterations in receptor-stimulated phosphoinositide hydrolysis in the hippocampus vary as a function of dose of colchicine.

The stimulation of inositol phospholipid (PI) hydrolysis by various receptor agonists was measured in the hippocampus of rats 12 weeks after various concentrations (0.5-2.0 microgram/site) of colchicine were infused into the dentate gyrus. Colchicine produced a dose-related decrease in the average width and length of the granule cell line; the pyramidal cells in CA1 and CA3 regions of the hippocampus were affected only at higher concentrations of colchicine. Compensatory increases in receptor-mediated hydrolysis of phosphoinositides (PI) in hippocampal slices were seen at 100 microns carbachol and ibotenic acid in rats receiving 1.5-3.5 microgram colchicine/site. Compensatory increases in norepinephrine (100 microns) and N-methyl-D-aspartate (100 microns) stimulated PI were seen at 2.5-3.5 and 3.5 micrograms colchicine/site, respectively. Compensatory increases in PI hydrolysis were not seen in slices from animals receiving 0.5 microgram colchicine/site. These data support the hypothesis that the signal transduction system in the hippocampus undergoes a compensatory change following experimentally induced destruction of dentate gyrus granule cells. In addition, these changes occur for more than one neurotransmitter and the alterations vary as a function of the size of the lesion.

Animals↗