Research in Experimental Medicine

, Volume 179, Issue 2, pp 153–161 | Cite as

Effects of clofibric acid and bezafibrate administration on activities of alkaline phosphatase and other enzymes in livers of rats

  • Autar K. Walli
  • D. Seidel
Original Contributions


Administration of clofibric acid and bezafibrate to rats lowers plasma lipids, increases the liver weight, and causes a slight decrease in the activity of alkaline phosphatase in plasma. However, both these drugs increase the activity of alkaline phosphatase in liver over threefold. The activity of other enzymes did not change by the same magnitude. The increase in the alkaline phosphatase activity in liver tissue appears to be due to increase in the activity of this enzyme in parenchymal cells. Clofibric acid and bezafibrate increase the activity of bilirubin-glucuronyl transferase activity over twofold in liver microsomes.

It is thus evident that both these drugs cause similar changes in various enzyme activities in liver even though bezafibrate has been reported to have a much shorter biologic halflife than clofibric acid.

Key words

Clofibric acid Bezafibrate Liver enzymes Alkaline phosphatase Bilirubin-glucuronyl transferase Hepatocytes 


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  1. Abshagen U, Bablok W, Koch K, Lang PD, Schmidt HAE, Stork H (1979) Disposition pharmacokinetics of bezafibrate in man. Eur J Clin Pharmacol 16:31–38PubMedGoogle Scholar
  2. Ahmed Z, King EJ (1959) Placental phosphatases. Biochim Biophys Acta 34:313–325PubMedGoogle Scholar
  3. Anthony L, Schmucker D, Mooney J, Jones A (1978) A quantitative analysis of fine structure and drug metabolism in livers of clofibrate-treated young adult and retired breeder rats. J Lipid Res 19:154–165PubMedGoogle Scholar
  4. Avoy DR, Swyrd EA, Gould RG (1965) Effects ofα-p-chlorophenoxyisobutyrylethyl ester (CPIB) with and without androsterone biosynthesis in liver. J Lipid Res 6:369–376Google Scholar
  5. Bergmeyer HU (1970) In: Methoden der enzymatischen Analyse, Vol I, II. Verlag Chemie, Weinheim, BergstraßeGoogle Scholar
  6. Berndt J, Gaumert R, Still J (1978) Mode of action of lipid-lowering agents, clofibrate and BM 15075 on cholesterol biosynthesis in rat liver. Atherosclerosis 30:147–152PubMedGoogle Scholar
  7. Berry MN, Friend DS (1969) High-yield preparation of isolated liver parenchymal cells. A biochemical and fine structural study. J Cell Biol 43:506–520PubMedGoogle Scholar
  8. Best MM, Duncan CH (1964) Hypolipemia and hepatomegaly from ethyl chlorophenoxyisobutyrate (CPIB) in the rat. J Lab Clin Med 64:634–642PubMedGoogle Scholar
  9. Bolzano K, Krempler F, Schellenberg B, Schlierf (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 134–136Google Scholar
  10. Burch RE, Curran GL (1969) Hepatic acetoacetyl-CoA deacylase activity in rats fed ethyl chlorophenoxyisobutyrate (CPIB). J Lipid Res 10:668–673PubMedGoogle Scholar
  11. Fahimi HD, Kalmbach P, Stegmeier K, Stork H (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 66–77Google Scholar
  12. Foliot A, Drocourt J-L, Etienne JP, Housset E, Fiessinger JN, Christoforov B (1977) Increase in the hepatic glucuronidation and clearance of bilirubin in clofibrate-treated rats. Biochem Pharmacol 26:547–549PubMedGoogle Scholar
  13. Gear RL, Albert AD, Bednarek (1974) The effect of hypocholesterolemic drug clofibrate on liver mitochondrial biogenesis. J Biol Chem 249:6495–6504PubMedGoogle Scholar
  14. Hellman L, Zumoff B, Kessler G, Kara E, Rubin IL, Rosenfeld RS (1963) Reduction of cholesterol and lipids in man by ethyl-chlorophenoxyisobutyrate. Ann Int Med 59:477–493PubMedGoogle Scholar
  15. Hess R, Stäubli W, Reiss W (1965) Nature of hepatomegalic effect produced by ethylchlorophenoxyisobutyrate in the rat. Nature 208:856–858PubMedGoogle Scholar
  16. Hodson AW, Latner AL, Raine L (1961) Isoenzymes of alkaline phosphatase. Clin Chim Acta 7:255–261Google Scholar
  17. Kaplan MM, Righetti A (1970) Induction of rat liver alkaline phosphatase, the mechanism of serum elevation in bile duct obstruction. J Clin Invest 49:508–516PubMedGoogle Scholar
  18. Lazarow P (1978) Rat liver peroxisomes catalyze theβ-oxidation of fatty acids. J Biol Chem 253:1522–1528PubMedGoogle Scholar
  19. Lazarow P (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 100–104Google Scholar
  20. Lazarow P, de-Duve C (1976) A fatty acyl-CoA oxidizing system in rat liver peroxisomes, enhancements by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci USA 73:2043–2046PubMedGoogle Scholar
  21. Lowry OH, Rosebrough NJ, Farr L, Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  22. Moss DW, Walli AK (1969) Intermediates in the hydrolysis of ATP by human alkaline phosphatase. Biochem Biophys Acta 191:476–477PubMedGoogle Scholar
  23. Nordlie RC, Arion WJ (1966) In: Colowick SP, Kaplan NO (eds) Methods in enzymology, vol 9. Academic Press, New York, p 619Google Scholar
  24. Omura T, Sato R (1964) The carbon monoxide binding pigment of liver microsomes. Solubilization, purification and its properties. J Biol Chem 239:2379–2385PubMedGoogle Scholar
  25. Platt DS, Thorp JM (1966) Changes in the weight and composition of liver in the rat, dog and monkey treated with chlorophenoxyisobutyrate. Biochem Pharmacol 15:915–925PubMedGoogle Scholar
  26. Posen S (1967) Alkaline phosphatase. Ann Int Med 67:183–202PubMedGoogle Scholar
  27. Reddy J, Krishnakantha T (1975) Hepatic peroxisome proliferation. Induction by two novel compounds structurally unrelated to clofibrate. Science 190:787–789PubMedGoogle Scholar
  28. Roy FP van, Heirwegh KPM (1968) Determination of bilirubin glucuronide and assay of glucuronyltransferase with bilirubin as acceptor. Biochem J 107:507–518PubMedGoogle Scholar
  29. Schade RWB, Demacker PNM, Van'T Laar A (1975) Reduction of serum alkaline phosphatase by clofibrate. Lancet I:862–863Google Scholar
  30. Schade RWB, Demacker PNM, Van'T Laar A (1977) Clofibrate effect on alkaline phosphatase. Bone or liver fraction. N Engl J Med 297:669Google Scholar
  31. Schimassek H (1963) Metabolite des Kohlenhydratstoffwechsels der isoliert perfundierten Rattenleber. Biochem Z 336:460–467PubMedGoogle Scholar
  32. Schimassek H, Hofer G, Walli AK (1971) In: Martini GA, Bode Ch (eds) Metabolic changes induced by alcohol. Springer, Heidelberg, pp 157–165Google Scholar
  33. Stegmeier K, Stork H, Lenz H, Leuschner F, Liede V (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 78–84Google Scholar
  34. Walli AK, Birkmann K, Schimassek H (1974) Glycogen metabolism in isolated rat parenchymal cells. Hoppe Seylers Z Physiol Chem 355:1264Google Scholar
  35. Walli AK, Schimassek H (1976) Glycogen metabolism in isolated parenchymal cells. In: Tager JM, Söling HD, Williamson JR (eds) Use of isolated liver cells and kidney tubules in metabolic studies. North Holland Publ Co, Amsterdam, pp 426–429Google Scholar
  36. Whitaker KB, Costa D, Moss DW (1979) Selective effects of clofibrate on alkaline phosphatase isoenzymes in serum. Clin Chim Acta 94:191–196PubMedGoogle Scholar
  37. White LW (1971) Regulation of hepatic cholesterol biosynthesis by clofibrate administration. J Pharmacol Exp Ther 178:361–370PubMedGoogle Scholar
  38. Wilkinson JH (1965) In: Isoenzymes. E & FN Spon Ltd, London, pp 104–119Google Scholar
  39. Wootton AM, Neale G, Moss DW (1975) Some properties of alkaline phosphatases in parenchymal and biliary tract cells separated from rat liver. Clin Chim Acta 61:183–190PubMedGoogle Scholar
  40. Zumoff B (1977) Effect of clofibrate on plasma levels of alkaline phosphatase. N Engl J Med 297:669Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Autar K. Walli
    • 1
  • D. Seidel
    • 1
  1. 1.Dept. of Clinical Chemistry, Center of Internal MedicineUniversity of GöttingenGöttingenFederal Republic of Germany

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