Summary
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.
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References
Abshagen U, Bablok W, Koch K, Lang PD, Schmidt HAE, Stork H (1979) Disposition pharmacokinetics of bezafibrate in man. Eur J Clin Pharmacol 16:31–38
Ahmed Z, King EJ (1959) Placental phosphatases. Biochim Biophys Acta 34:313–325
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 19:154–165
Avoy DR, Swyrd EA, Gould RG (1965) Effects ofα-p-chlorophenoxyisobutyrylethyl ester (CPIB) with and without androsterone biosynthesis in liver. J Lipid Res 6:369–376
Bergmeyer HU (1970) In: Methoden der enzymatischen Analyse, Vol I, II. Verlag Chemie, Weinheim, Bergstraße
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 30:147–152
Berry MN, Friend DS (1969) High-yield preparation of isolated liver parenchymal cells. A biochemical and fine structural study. J Cell Biol 43:506–520
Best MM, Duncan CH (1964) Hypolipemia and hepatomegaly from ethyl chlorophenoxyisobutyrate (CPIB) in the rat. J Lab Clin Med 64:634–642
Bolzano K, Krempler F, Schellenberg B, Schlierf (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 134–136
Burch RE, Curran GL (1969) Hepatic acetoacetyl-CoA deacylase activity in rats fed ethyl chlorophenoxyisobutyrate (CPIB). J Lipid Res 10:668–673
Fahimi HD, Kalmbach P, Stegmeier K, Stork H (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 66–77
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 26:547–549
Gear RL, Albert AD, Bednarek (1974) The effect of hypocholesterolemic drug clofibrate on liver mitochondrial biogenesis. J Biol Chem 249:6495–6504
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 59:477–493
Hess R, Stäubli W, Reiss W (1965) Nature of hepatomegalic effect produced by ethylchlorophenoxyisobutyrate in the rat. Nature 208:856–858
Hodson AW, Latner AL, Raine L (1961) Isoenzymes of alkaline phosphatase. Clin Chim Acta 7:255–261
Kaplan MM, Righetti A (1970) Induction of rat liver alkaline phosphatase, the mechanism of serum elevation in bile duct obstruction. J Clin Invest 49:508–516
Lazarow P (1978) Rat liver peroxisomes catalyze theβ-oxidation of fatty acids. J Biol Chem 253:1522–1528
Lazarow P (1979) In: Greten H, Lang PD, Schettler G (Hrsg) Lipoproteine und Herzinfarkt. Witzstrock, Baden-Baden, S 100–104
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 73:2043–2046
Lowry OH, Rosebrough NJ, Farr L, Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275
Moss DW, Walli AK (1969) Intermediates in the hydrolysis of ATP by human alkaline phosphatase. Biochem Biophys Acta 191:476–477
Nordlie RC, Arion WJ (1966) In: Colowick SP, Kaplan NO (eds) Methods in enzymology, vol 9. Academic Press, New York, p 619
Omura T, Sato R (1964) The carbon monoxide binding pigment of liver microsomes. Solubilization, purification and its properties. J Biol Chem 239:2379–2385
Platt DS, Thorp JM (1966) Changes in the weight and composition of liver in the rat, dog and monkey treated with chlorophenoxyisobutyrate. Biochem Pharmacol 15:915–925
Posen S (1967) Alkaline phosphatase. Ann Int Med 67:183–202
Reddy J, Krishnakantha T (1975) Hepatic peroxisome proliferation. Induction by two novel compounds structurally unrelated to clofibrate. Science 190:787–789
Roy FP van, Heirwegh KPM (1968) Determination of bilirubin glucuronide and assay of glucuronyltransferase with bilirubin as acceptor. Biochem J 107:507–518
Schade RWB, Demacker PNM, Van'T Laar A (1975) Reduction of serum alkaline phosphatase by clofibrate. Lancet I:862–863
Schade RWB, Demacker PNM, Van'T Laar A (1977) Clofibrate effect on alkaline phosphatase. Bone or liver fraction. N Engl J Med 297:669
Schimassek H (1963) Metabolite des Kohlenhydratstoffwechsels der isoliert perfundierten Rattenleber. Biochem Z 336:460–467
Schimassek H, Hofer G, Walli AK (1971) In: Martini GA, Bode Ch (eds) Metabolic changes induced by alcohol. Springer, Heidelberg, pp 157–165
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 78–84
Walli AK, Birkmann K, Schimassek H (1974) Glycogen metabolism in isolated rat parenchymal cells. Hoppe Seylers Z Physiol Chem 355:1264
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 426–429
Whitaker KB, Costa D, Moss DW (1979) Selective effects of clofibrate on alkaline phosphatase isoenzymes in serum. Clin Chim Acta 94:191–196
White LW (1971) Regulation of hepatic cholesterol biosynthesis by clofibrate administration. J Pharmacol Exp Ther 178:361–370
Wilkinson JH (1965) In: Isoenzymes. E & FN Spon Ltd, London, pp 104–119
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 61:183–190
Zumoff B (1977) Effect of clofibrate on plasma levels of alkaline phosphatase. N Engl J Med 297:669
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Walli, A.K., Seidel, D. Effects of clofibric acid and bezafibrate administration on activities of alkaline phosphatase and other enzymes in livers of rats. Res. Exp. Med. 179, 153–161 (1981). https://doi.org/10.1007/BF01851983
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DOI: https://doi.org/10.1007/BF01851983