Effect of colchicine and trimethylcolchicinic acid on CCl4-induced cirrhosis in the rat

Pharmacol Toxicol. 1996 Nov;79(5):241-6. doi: 10.1111/j.1600-0773.1996.tb00267.x.

Abstract

Colchicine is one of the most promising drugs for the treatment of cirrhosis. However, due to its toxicity, other drugs are being evaluated and colchicine-like molecules may be good alternatives. The aim of this work was to compare the beneficial effects of colchicine and trimethylcolchicinic acid (a colchicinoid less toxic than colchicine) on CCl4-cirrhosis. The drugs were administered either through CCl4 administration (8 weeks) or after CCl4 intoxication for 4 weeks at a dose of 10 micrograms/rat/day, orally. Liver plasma membranes were isolated for high affinity Ca(2+)-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase activities. The activities of gamma-glutamyl transpeptidase and alkaline phosphatase were also measured in serum. Liver glycogen content and a marker for lipid peroxidation were determined in liver samples. We found that both compounds preserved and significantly reversed high affinity Ca(2+)-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase plasma membrane and serum enzyme activities as well as the hepatic glycogen content.

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / metabolism
  • Alkaline Phosphatase / blood
  • Alkaline Phosphatase / metabolism
  • Animals
  • Aspartate Aminotransferases / blood
  • Aspartate Aminotransferases / metabolism
  • Calcium-Transporting ATPases / metabolism
  • Carbon Tetrachloride Poisoning / drug therapy*
  • Carbon Tetrachloride Poisoning / enzymology
  • Carbon Tetrachloride Poisoning / pathology
  • Cell Membrane / enzymology
  • Colchicine / analogs & derivatives*
  • Colchicine / therapeutic use
  • Lipid Peroxidation / drug effects
  • Liver / pathology
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / enzymology
  • Liver Cirrhosis, Experimental / pathology
  • Liver Glycogen / metabolism
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Liver Glycogen
  • trimethylcolchicinic acid
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Calcium-Transporting ATPases
  • Colchicine