Neuroscience. 2002;113(2):253-6.
Regionally selective neurotoxicity of NMDA and colchicine is independent of hippocampal neural circuitry.

Ikegaya Y, Matsuki N.

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ikegayk.airnet.ne.jp

The mechanisms by which cerebral ischemia and several neurotoxins cause regionally selective damages to the hippocampal formation are largely unknown. The CA1-selective toxicity of N-methyl--aspartate (NMDA), the CA3-selective toxicity of kainate, and the dentate gyrus (DG)-selective toxicity of colchicine were observed in organotypic entorhino-hippocampal cultures. The selective neurotoxicity of NMDA and colchicine but not kainate was present in isolated tissue cultures of each hippocampal subregion, suggesting that the regional vulnerability is irrespective of the hippocampal trisynaptic pathway. Dispersed cultures of neurons prepared from Ammon's horn and the DG still exhibited a preference for susceptibility to NMDA and colchicine, respectively. Thus, the neurons per se appear to be inherently susceptible to specific toxins independently of their original loci, intrinsic neural circuits, vascular system, or other systemic factors.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12127083&dopt=Abstract colchicine



Pharmacol Biochem Behav. 2002 Oct;73(3):565-71.
Intracerebroventricular administration of colchicine produces cognitive impairment associated with oxidative stress in rats.

Veerendra Kumar MH, Gupta YK.

Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

Oxidative stress has been implicated in neurodegenerative disorders including the Alzheimer's disease (AD). Central administration of colchicine is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. However, it is not known whether this cognitive impairment is associated with free radical generation. Therefore, in the present study, the effect of intracerebroventricular colchicine was studied on paradigms of learning and memory behavior and the markers of oxidative stress in rats. Adult male Wistar rats (200-250 g) were injected with colchicine (intracerebroventricular) bilaterally (15 microg/rat; 7.5 microg/site) on the first day. The learning and memory behavior was assessed using passive avoidance paradigm, elevated plus maze and closed field activity test on Days 13, 14 and 21. The parameters of oxidative stress were assessed by measuring the malondialdehyde (MDA), glutathione, superoxide dismutase (SOD) and catalase levels in brain tissue on Day 21 of the colchicine injection. The rats developed significant learning and memory impairment as indicated by deficit in behavioral paradigms. There was a significant elevation in MDA levels and decrease in levels of glutathione. No significant difference was observed in SOD and catalase levels. Thus, the study demonstrates that central administration of colchicine causes impairment in learning and memory with associated increase in oxidative stress.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151031&dopt=Abstract colchicine



Lung. 2002;180(2):61-72.
Mechanisms of colchicine effect in the treatment of asbestosis and idiopathic pulmonary fibrosis.

Addrizzo-Harris DJ, Harkin TJ, Tchou-Wong KM, McGuinness G, Goldring R, Cheng D, Rom DW.

Bellevue Chest Service, Division of Pulmonary and Critical Care Medicine, Department of Medicine, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.

The objective of this study was to evaluate the mechanisms of colchicine action in pulmonary fibrosis. The study included 10 patients with pulmonary fibrosis (idiopathic pulmonary fibrosis 5, asbestosis 4, and scleroderma 1) who had been admitted to Bellevue Hospital Center, a tertiary care public hospital in New York City. We administered colchicine 0.6 mg orally for 12 weeks to patients with pulmonary fibrosis. Symptoms, high resolution CT scans, pulmonary function tests, and bronchoalveolar lavage parameters were compared prior to and after treatment. Results showed declines in dyspnea index, selective improvement in several CT scans, but no statistically significant change in BAL cells, cytokines, fibronectin, or hydroxyproline. However, there was a decline in hydroxyproline in the BAL fluid in 8/10 patients. We concluded that colchicine has a mild antifibrotic effect which may be in inhibiting collagen formation since there was no effect on the inflammation that accompanies fibrosis.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12172901&dopt=Abstract colchicine



Biochemistry. 1999 Apr 20;38(16):5082-8.
Quantitative characterization of the binding of fluorescently labeled colchicine to tubulin in vitro using fluorescence correlation spectroscopy.

Van Craenenbroeck E, Engelborghs Y.

Laboratory of Biomolecular Dynamics, University of Leuven, Heverlee, Belgium.

Fluorescence correlation spectroscopy (FCS) is a new technique that allows the determination of the diffusion constant of a fluorescent molecule in solution. Also, the binding of the fluorescent molecule to a target can be analyzed, if the difference in the diffusion coefficients of the free and bound ligand is sufficiently large. With FCS, the interaction between fluorescein-colchicine (FC) and tubulin has been studied in vitro. A fast and reversible binding is observed with an association constant at room temperature of (3.9 +/- 0.1) x 10(4) M-1. No competition with colchicine is seen, indicating that FCS reveals the existence of a new binding site on tubulin. FCS is not able to show the binding of FC to the original colchicine binding site, even though it exists, because the fluorescence of FC is strongly quenched upon binding to this site. This quenching is evident in spectrofluorometry experiments, revealing a slow binding of FC to tubulin that is subject to competition with colchicine. FCS allows the determination of the diffusion coefficients of both free and bound fluorescent colchicine which were found to be (2.6 +/- 0.2) x 10(-)10 and (2.0 +/- 0.2) x 10(-)11 m2 s-1, respectively. It can be concluded that fluorescent labeling, especially of small molecules, can interfere considerably with the binding behavior that is being studied. Although general qualitative effects in vivo are similar for colchicine and its fluorescein derivative, this quantitative study of the binding to tubulin presents a nuanced view, and the existence of a second binding site for FC can even explain some conflicting indications in the literature.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10213611&dopt=Abstract colchicine