Skip to main content
PMC home page
Gut logoLink to Gut
. 1993 Oct;34(10):1438–1442. doi: 10.1136/gut.34.10.1438

Reversal of carbon tetrachloride induced changes in microviscosity and lipid composition of liver plasma membrane by colchicine in rats.

J A Solis-Herruzo 1, M De Gando 1, M P Ferrer 1, I Hernandez Muñoz 1, B Fernandez-Boya 1, M P De la Torre 1, M T Muñoz-Yague 1
PMCID: PMC1374558  PMID: 8244117

Abstract

Colchicine is beneficial in the treatment of cirrhotic patients, it prevents changes in plasma membrane bound enzymes induced by CCl4 intoxication. In this study, lipid composition and microviscosity were measured in liver plasma membranes isolated from rats given CCl4. Microviscosity values increased in rats given CCl4 for six weeks but fell considerably in those given CCl4 for 10 weeks. Both these changes were absent when colchicine was given with CCl4. The cholesterol/phospholipid molar ratios and lipid peroxide values increased but plasma membrane phospholipids, the length of fatty acyl chains, and the unsaturation index fell significantly after CCl4 intoxication. Colchicine treatment also prevented these changes. Changes in the lipid composition of liver plasma membranes were significantly correlated with lipid peroxidation. Colchicine prevents changes in the physicochemical properties of liver plasma membranes induced by longterm CCl4 treatment, probably by blocking peroxidation of unsaturated fatty acids.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alvaro D., Angelico M., Attili A. F., De Santis A., Piéche U., Capocaccia L. Abnormalities in erythrocyte membrane phospholipids in patients with liver cirrhosis. Biochem Med. 1982 Oct;28(2):157–164. doi: 10.1016/0006-2944(82)90066-7. [DOI] [PubMed] [Google Scholar]
  2. Aszalos A., Yang G. C., Gottesman M. M. Depolymerization of microtubules increases the motional freedom of molecular probes in cellular plasma membranes. J Cell Biol. 1985 May;100(5):1357–1362. doi: 10.1083/jcb.100.5.1357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. Benedetti A., Marucci L., Ferretti G., Curatola G., Jézéquel A. M., Orlandi F. Evidence that plasma membrane fluidity of isolated hepatocytes is modified by exposure to microtubule-depolymerizing drugs. J Hepatol. 1990 Mar;10(2):144–148. doi: 10.1016/0168-8278(90)90043-q. [DOI] [PubMed] [Google Scholar]
  6. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  7. Bruch R. C., Thayer W. S. Differential effect of lipid peroxidation on membrane fluidity as determined by electron spin resonance probes. Biochim Biophys Acta. 1983 Sep 7;733(2):216–222. doi: 10.1016/0005-2736(83)90525-4. [DOI] [PubMed] [Google Scholar]
  8. Cairns S. R., Peters T. J. Biochemical analysis of hepatic lipid in alcoholic and diabetic and control subjects. Clin Sci (Lond) 1983 Dec;65(6):645–652. doi: 10.1042/cs0650645. [DOI] [PubMed] [Google Scholar]
  9. Cerbon J., Noriega M., Rojkind M. Increased stimulation of alkaline phosphatase by small doses of colchicine entrapped in liposomes. A biochemical test to detect effective liposome-hepatocyte interaction. Biochem Pharmacol. 1986 Nov 1;35(21):3799–3803. doi: 10.1016/0006-2952(86)90667-2. [DOI] [PubMed] [Google Scholar]
  10. Coleman R., Michell R. H., Finean J. B., Hawthorne J. N. A purified plasma membrane fraction isolated from rat liver under isotonic conditions. Biochim Biophys Acta. 1967 Sep 9;135(4):573–579. doi: 10.1016/0005-2736(67)90089-2. [DOI] [PubMed] [Google Scholar]
  11. DE DUVE C., PRESSMAN B. C., GIANETTO R., WATTIAUX R., APPELMANS F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955 Aug;60(4):604–617. doi: 10.1042/bj0600604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Deliconstantinos G., Mykoniatis M., Papadimitriou D. Carbon tetrachloride modulates the rat hepatic microsomal UDP-glucuronyl transferase activity and membrane fluidity. Experientia. 1986 Feb 15;42(2):181–183. doi: 10.1007/BF01952457. [DOI] [PubMed] [Google Scholar]
  13. Diegelmann R. F., Peterkofsky B. Inhibition of collagen secretion from bone and cultured fibroblasts by microtubular disruptive drugs. Proc Natl Acad Sci U S A. 1972 Apr;69(4):892–896. doi: 10.1073/pnas.69.4.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dinarello C. A., Chusid M. J., Fauci A. S., Gallin J. I., Dale D. C., Wolff S. M. Effect of prophylactic colchicine therapy on leukocyte function in patients with familial Mediterranean fever. Arthritis Rheum. 1976 May-Jun;19(3):618–622. doi: 10.1002/art.1780190315. [DOI] [PubMed] [Google Scholar]
  15. EMMELOT P., BOS C. J., BENEDETTI E. L., RUEMKE P. STUDIES ON PLASMA MEMBRANES. I. CHEMICAL COMPOSITION AND ENZYME CONTENT OF PLASMA MEMBRANES ISOLATED FROM RAT LIVER. Biochim Biophys Acta. 1964 Jul 15;90:126–145. doi: 10.1016/0304-4165(64)90125-4. [DOI] [PubMed] [Google Scholar]
  16. Ellinger A., Pavelka M., Gangl A. Effect of colchicine on rat small intestinal absorptive cells. II. Distribution of label after incorporation of [3H]fucose into plasma membrane glycoproteins. J Ultrastruct Res. 1983 Dec;85(3):260–271. doi: 10.1016/s0022-5320(83)90038-2. [DOI] [PubMed] [Google Scholar]
  17. Harris E. D., Jr, Krane S. M. Effects of colchicine on collagenase in cultures of rheumatoid synovium. Arthritis Rheum. 1971 Nov-Dec;14(6):669–684. doi: 10.1002/art.1780140602. [DOI] [PubMed] [Google Scholar]
  18. Jähnig F. Structural order of lipids and proteins in membranes: evaluation of fluorescence anisotropy data. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6361–6365. doi: 10.1073/pnas.76.12.6361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kershenobich D., Uribe M., Suárez G. I., Mata J. M., Pérez-Tamayo R., Rojkind M. Treatment of cirrhosis with colchicine. A double-blind randomized trial. Gastroenterology. 1979 Sep;77(3):532–536. [PubMed] [Google Scholar]
  20. Kershenobich D., Vargas F., Garcia-Tsao G., Perez Tamayo R., Gent M., Rojkind M. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med. 1988 Jun 30;318(26):1709–1713. doi: 10.1056/NEJM198806303182602. [DOI] [PubMed] [Google Scholar]
  21. Landon E. J., Jaiswal R. K., Naukam R. J., Sastry B. V. Effects of calcium channel blocking agents on membrane microviscosity and calcium in the liver of the carbon tetrachloride treated rat. Biochem Pharmacol. 1984 Nov 15;33(22):3553–3560. doi: 10.1016/0006-2952(84)90136-9. [DOI] [PubMed] [Google Scholar]
  22. Lentz B. R., Moore B. M., Barrow D. A. Light-scattering effects in the measurement of membrane microviscosity with diphenylhexatriene. Biophys J. 1979 Mar;25(3):489–494. doi: 10.1016/S0006-3495(79)85318-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mourelle M., Meza M. A. Colchicine prevents D-galactosamine-induced hepatitis. J Hepatol. 1989 Mar;8(2):165–172. doi: 10.1016/0168-8278(89)90004-4. [DOI] [PubMed] [Google Scholar]
  24. Mourelle M., Villalon C., Amezcua J. L. Protective effect of colchicine on acute liver damage induced by carbon tetrachloride. J Hepatol. 1988 Jun;6(3):337–342. doi: 10.1016/s0168-8278(88)80051-5. [DOI] [PubMed] [Google Scholar]
  25. NEVILLE D. M., Jr The isolation of a cell membrane fraction from rat liver. J Biophys Biochem Cytol. 1960 Oct;8:413–422. doi: 10.1083/jcb.8.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Oda K., Misumi Y., Ikehara Y. Disparate effects of monensin and colchicine on intracellular processing of secretory proteins in cultured rat hepatocytes. Eur J Biochem. 1983 Sep 15;135(2):209–216. doi: 10.1111/j.1432-1033.1983.tb07639.x. [DOI] [PubMed] [Google Scholar]
  27. Ohkawa H., Ohishi N., Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979 Jun;95(2):351–358. doi: 10.1016/0003-2697(79)90738-3. [DOI] [PubMed] [Google Scholar]
  28. Otani H., Prasad M. R., Jones R. M., Das D. K. Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts. Am J Physiol. 1989 Jul;257(1 Pt 2):H252–H258. doi: 10.1152/ajpheart.1989.257.1.H252. [DOI] [PubMed] [Google Scholar]
  29. Reaven E., Azhar S. Effect of various hepatic membrane fractions on microtubule assembly-with special emphasis on the role of membrane phospholipids. J Cell Biol. 1981 May;89(2):300–308. doi: 10.1083/jcb.89.2.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rojkind M., Uribe M., Kershenobich D. Colchicine and the treatment of liver cirrhosis. Lancet. 1973 Jan 6;1(7793):38–39. [PubMed] [Google Scholar]
  31. Schachter D. Fluidity and function of hepatocyte plasma membranes. Hepatology. 1984 Jan-Feb;4(1):140–151. doi: 10.1002/hep.1840040124. [DOI] [PubMed] [Google Scholar]
  32. Schuller A., Solis-Herruzo J. A., Moscat J., Fernandez-Checa J. C., Municio A. M. The fluidity of liver plasma membranes from patients with different types of liver injury. Hepatology. 1986 Jul-Aug;6(4):714–717. doi: 10.1002/hep.1840060429. [DOI] [PubMed] [Google Scholar]
  33. Schüller A., Moscat J., Diez E., Fernandez-Checa C., Gavilanes F. G., Municio A. M. The fluidity of plasma membranes from ethanol-treated rat liver. Mol Cell Biochem. 1984 Sep;64(1):89–95. doi: 10.1007/BF00420932. [DOI] [PubMed] [Google Scholar]
  34. Sevanian A., Stein R. A., Mead J. F. Metabolism of epoxidized phosphatidylcholine by phospholipase A2 and epoxide hydrolase. Lipids. 1981 Nov;16(11):781–789. doi: 10.1007/BF02535029. [DOI] [PubMed] [Google Scholar]
  35. Shiba M., Watanabe E., Sasakawa S., Ikeda Y. Effects of taxol and colchicine on platelet membrane properties. Thromb Res. 1988 Nov 15;52(4):313–323. doi: 10.1016/0049-3848(88)90072-2. [DOI] [PubMed] [Google Scholar]
  36. Shinitzky M., Barenholz Y. Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta. 1978 Dec 15;515(4):367–394. doi: 10.1016/0304-4157(78)90010-2. [DOI] [PubMed] [Google Scholar]
  37. Spector A. A., Yorek M. A. Membrane lipid composition and cellular function. J Lipid Res. 1985 Sep;26(9):1015–1035. [PubMed] [Google Scholar]
  38. Tijburg L. B., Geelen M. J., van Golde L. M. Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine in the liver. Biochim Biophys Acta. 1989 Jul 17;1004(1):1–19. doi: 10.1016/0005-2760(89)90206-3. [DOI] [PubMed] [Google Scholar]
  39. Yahuaca P., Amaya A., Rojkind M., Mourelle M. Cryptic adenosine triphosphatase activities in plasma membranes of CCl4-cirrhotic rats. Its modulation by changes in cholesterol/phospholipid ratios. Lab Invest. 1985 Nov;53(5):541–545. [PubMed] [Google Scholar]
  40. Yeagle P. L. Lipid regulation of cell membrane structure and function. FASEB J. 1989 May;3(7):1833–1842. [PubMed] [Google Scholar]
  41. ZLATKIS A., ZAK B., BOYLE A. J. A new method for the direct determination of serum cholesterol. J Lab Clin Med. 1953 Mar;41(3):486–492. [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES