Effects of oral administration of bezafibrate on peroxisomes and carnitine acetyltransferase in rat hepatocytes.

Changes in fine structure of peroxisomes and mitochondria were examined by electron microscopy in the hepatocyte of rats administered with bezafibrate, a hypolipidemic reagents. Peroxisomes increased to approximately 4.8 times in number one week after oral administration of bezafibrate in male rats. Newly induced peroxisomes showed paler matrix with frequent absence of core structure at two weeks after administration, peroxisomes further increased in number, 5.8 times in males, and were mostly devoid of core structure. Mitochondrial cristae were occasionally arranged along the long axis of mitochondria. Activity of carnitine acetyltransferase (CAT), one of the enzymes involved in beta oxidation of fatty acids, increased significantly after oral administration of bezafibrate. At two weeks after administration, it increased up to 12.0 times in males, 8.4 times in castrated males, 3.8 times in females and 5.5 times in castrated females, respectively. Cytochemically, CAT was localized in the outer compartment and inner membrane of mitochondria. CAT activity was also detected in the matrix of peroxisomes at two weeks after oral administration of bezafibrate.

[1]  D. Valle,et al.  The 70 kDa peroxisomal membrane protein: an ATP-binding cassette transporter protein involved in peroxisome biogenesis. , 1993, Seminars in cell biology.

[2]  R Kato,et al.  Sex-specific cytochrome P450 as a cause of sex- and species-related differences in drug toxicity. , 1992, Toxicology letters.

[3]  H. Takebe Morphological changes in the hepatocyte peroxisomes by age in mice administered with an anti-hyperlipidemic agent,clofibrte , 1992 .

[4]  K. Alberti,et al.  Clofibrate induces carnitine acyltransferases in periportal and perivenous zones of rat liver and does not disturb the acinar zonation of gluconeogenesis. , 1989, Biochimica et biophysica acta.

[5]  Yamada Junji,et al.  Species differences in the effects of bezafibrate, a hypolipidemic agent, on hepatic peroxisome-associated enzymes. , 1989 .

[6]  K. Beier,et al.  Selective induction of peroxisomal enzymes by the hypolipidemic drug bezafibrate. Detection of modulations by automatic image analysis in conjunction with immunoelectron microscopy and immunoblotting. , 1988, European journal of cell biology.

[7]  C. Henninger,et al.  Effects of fenofibrate treatment on fatty acid oxidation in liver mitochondria of obese Zucker rats. , 1987, Biochemical pharmacology.

[8]  J. Bar-Tana,et al.  Adipocyte conversion of cultured 3T3-L1 preadipocytes by bezafibrate. , 1987, Life sciences.

[9]  J. Bar-Tana,et al.  Adipose conversion of cultured rat primary preadipocytes by hypolipidemic drugs. , 1986, Biochimica et biophysica acta.

[10]  T. Kamataki,et al.  Postnatal development of constitutive forms of cytochrome P-450 in liver microsomes of male and female rats. , 1984, Biochemical pharmacology.

[11]  T. Kamataki,et al.  Sex difference of cytochrome P-450 in the rat: purification, characterization, and quantitation of constitutive forms of cytochrome P-450 from liver microsomes of male and female rats. , 1983, Archives of biochemistry and biophysics.

[12]  P. Lazarow Catabolic Functions of Peroxisomes: Modification by Hypoupidemic Drugs , 1983 .

[13]  T. Hashimoto,et al.  Purification and properties of carnitine acetyltransferase from rat liver. , 1983, Journal of biochemistry.

[14]  A. Reinicke,et al.  THE SHORT‐ AND LONG‐TERM EFFECTS OF BEZAFIBRATE IN THE RAT * , 1982, Annals of the New York Academy of Sciences.

[15]  B. Lake,et al.  Peroxisome proliferation in cultured rat hepatocytes produced by clofibrate and phthalate ester metabolites. , 1982, Toxicology letters.

[16]  J. Reddy,et al.  Immunochemical identity of peroxisomal enoyl-CoA hydratase with the peroxisome-proliferation -associated 80,000 mol wt polypeptide in rat liver , 1981, The Journal of cell biology.

[17]  J. Reddy,et al.  Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens , 1980, Nature.

[18]  N. Tolbert,et al.  Comparison of the carnitine acyltransferase activites from rat liver peroxisomes and microsomes. , 1976, Archives of biochemistry and biophysics.

[19]  N. Tolbert,et al.  The subcellular distribution of carnitine acyltransferases in mammalian liver and kidney. A new peroxisomal enzyme. , 1973, The Journal of biological chemistry.

[20]  Svoboda Dj,et al.  Effects of selected hypolipidemic drugs on cell ultrastructure. , 1971 .

[21]  R. Barrnett,et al.  Cytochemical localization of transferase activities: carnitine acetyltransferase. , 1970, Journal of cell science.

[22]  M. Chiga,et al.  MICROBODIES IN EXPERIMENTALLY ALTERED CELLS , 1970, The Journal of cell biology.

[23]  R. Hess,et al.  NATURE OF THE HEPATOMEGALIC EFFECT PRODUCED BY ETHYL-CHLOROPHENOXY-ISOBUTYRATE IN THE RAT , 1965, Nature.