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Research Article

Extraperoxisomal Targets of Peroxisome Proliferators: Mitochondrial, Microsomal, and Cytosolic Effects. Implications for Health and Disease

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Pages 1-33 | Published online: 29 Sep 2008

References

  • Lazarow, P. and Fujiki, Y., Biogenesis of per-oxisomes, Ann. Rev. Cell Biol., 1985; 1: 489– 530.
  • Bentley, P., Elcombe, C., Grasso, P., Stringer, D., and Wiegand, H., Hepatic peroxisome proliferation in rodents and its significance for humans, Fd. Chem. Toxicol., 1993; 31: 857– 907.
  • Staubli, R., Hess, R., and Weibel, E., Correlated morphometric and biochemical studies on the rat liver cell. II. Effects of phenobarbital on rat hepatocytes, J. Cell. Biol., 1969; 42: 92–112.
  • Weibel, E., Staubli, W., Gangi, H., and Hess, F., Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods, and normal morpho-metric data for rat liver, J. Cell Biol., 1969; 42: 68–91.
  • Schutgens, R., Heyman, H., Wanders, R., Vandenbosch, H., and Tager, J. Peroxisomal disorders: A newly recognized group of genet-ic diseases, Eur. J. Pediatr., 1986; 144: 430– 440.
  • Tolbert, N., Metabolic pathways in peroxi-somes and glyxysomes, Ann. Rev. Biochem., 1981; 50: 133–157.
  • Xu, L., Ash, M., Abdel-aleem, S., Lowe, J., and Badr, M. Hyperinsulinemia inhibits hepatic peroxisomal b-oxidation in rats, Horm. Metab. Res., 1995; 27: 76–78.
  • Singh, I., Biochemistry of peroxisomes in health and disease, Mol. Cell. Biochem., 1997; 167: 1–29.
  • Paget, G., Experimental studies of the toxic-ity of atromid with particular reference to fine structural changes in the livers of rodents, J. Atheroscler. Res., 1963; 3: 729–736.
  • Oesch, F., Schladt, L., Steinberg, P., and Thomas, H. Concomitant induction of cytosolic epoxide hydrolase and peroxisomal b-oxidation by hy-polipidemic compounds in rat and guinea pig liver, Arch. Toxicol., 1988; 12 (Suppl): 248– 255.
  • Eacho, P., Foxworthy, P., Johnson, W., Hoover, D. and White, S. Hepatic peroxisomal changes induced by a tetrazole-substituted alkoxyacet-ophenone in rats and comparison with other species, Toxicol. Appl. Pharmacol., 1986; 83: 430–437.
  • Lake, B., Evans, J., Gray, T., Korosi, S., and North, C., Comparative studies on nafenopin-induced hepatic peroxisome proliferation in the rat, Syrian hamster, guinea pig and marmoset, Toxicol. Appl. Pharmacol., 1989; 99: 148– 160.
  • Watanabe, T., Horie, S., Yamada, J., Isaji, M., Nishigaki, T., Naito J., and Suga, T., Species differences in the effect of bezafibrate, a hypo-lipidemic agent, on hepatic peroxisome-asso-ciated enzymes, Biochem. Pharmacol., 1989; 38: 367–371.
  • De la Iglesia, F., Lewis, J., Buchanan, R., Marcus E., and Mc Mahon, G., Light and electron microscopy of liver in hyperlipoproteine-mic patients under long-term gemfibrozil treatment, Atherosclerosis, 1982; 43: 19–37.
  • Sakuma, M., Yamada, J., and Suga, T., Comparison of the inducing effect of dehydroepi-androsterone on hepatic peroxisome proliferation-associated enzymes in several rodent species, Biochem. Pharmacol., 1992; 43: 1269– 1273.
  • Bronfman, M., Amigo, L., and Morales, M., Activation of hypolipidaemic drugs to acyl-co-enzyme A thioesters, Biochem J., 1986; 239: 781–784.
  • Hertz, R. and Bar-Tana, J., The acylation of proteins by xenobiotic amphipathic carboxy-lic acid in cultured rat hepatocytes, Biochem. J., 1988; 254: 39–44.
  • Bronfman, M., Orellana, A., Morales, M., Bieri, F., Waechter, F., Staubli, W., and Bentley, P., Potentiation of diacylglycerol-activated protein kinase C by acyl-coenzyme A thioesters of hypolipidemic drugs, Biochem. Biophys. Res. Commun., 1989; 159: 1026–1031.
  • Horie, S., Fukumori, N., and Suga, T., Induction of hepatic peroxisomes by a new, non-carboxylate-containing drug, bifonazole, Toxicol. Lett., 1991; 55: 249–254.
  • Ram, P. and Waxman, D., Dehydroepiandros-terone 3b-sulfate is an endogenous activator of the peroxisome-proliferation pathway: induction of cytochrome P-450 and acyl-CoA oxidase mRNA in primary rat hepatocyte culture and inhibitory effects of Ca2+-channel block-ers, Biochem. J., 1994; 301: 753–758.
  • Horie, S., Ishii, H., and Suga, T., Changes in peroxisomal fatty acid oxidation in the diabetic rat liver, J. Biochem., 1981; 90: 1691– 1696.
  • Thomas, H., Schladt, L., Knehr M., and Oesch, F., Effect of diabetes and starvation on the activity of rat liver epoxide hydrolase, glutath-ione-S-transferase and peroxisomal b-oxidation, Biochem. Pharmacol., 1989; 38: 4291– 4297.
  • Fringes, B. and Reith, A., Time-course of peroxi-some biogenesis during adaptation to mild hy-perthyroidism in rat liver, Lab. Invest., 1982; 47: 19–26.
  • Fringes, B., Reith, A., and Riede, U., Peroxi-some biogenesis in rat liver during adaptation to mild hyperthyroidism: a morphometric/ster-eologic study by electron microscopy, Ann. N. Y. Acad. Sci. (USA), 1982; 386: 514–518.
  • Levy, E., Slusser, R., and Ruebner, B., Hepatic changes produced by a single dose of endotox-in in the mouse, Am. J. Path., 1968; 52: 477– 502.
  • Neat, C., Thomassen, M., and Osmundsen, H. Induction of peroxisomal b-oxidation in rat liver by a high-fat diet, Biochem. J., 1980; 186: 369–371.
  • Issemann, I. and Green, S., Activation of a member of the steroid hormone receptor super-family by peroxisome proliferators, Nature, 1990; 347: 645–650.
  • Tsai, M. and O’Malley, B. Molecular mechanisms of action of steroid/thyroid receptor super-family members, Ann. Rev. Biochem., 1994; 63: 451–486.
  • Gottlicher, M., Widmark, E., Li, Q., and Gustafsson, J.-A., Fatty acids activate a chimra of the clofibric acid-activated receptor and the glucocorticoid receptor, Proc. Natl. Acad. Sci. (USA), 1992; 89: 4653–4657.
  • Kliewer, S., Forman, B., Blumberg, B., Ong, E., Borgmeyer, U., Mangelsdorf, D., Umesono, K., and Evans, R., Differential expression and activation of a family of murine peroxisome prolif-erator-activated receptors, Proc. Natl. Acad. Sci. (USA), 1994; 91: 7344–7349.
  • Kliewer, S., Sundseth, S., Jones, S., Brown, P., Wisely, G. B., Koble, C., Devchand, P., Wahli, W., Wilson, T., Lenhard, J., and Lehman, J., Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxi-some proliferator-activated receptors a and g, Proc. Natl. Acad. Sci. (USA), 1997; 94: 4318– 4323.
  • Tontonoz, P., Singer, S., Forman, B., Sarraf, P., Fletcher, J., Fletcher, C., Brun, R., Mueller, E., Altoik, S., Oppenheim, H., Evans, R., and Spiegelman, B., Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptors g and the retinoid X receptor, Proc. Natl. Acad. Sci. (USA), 1997; 94: 237–241.
  • Devchand, P., Keller, H., Peters, J., Vazquez, M., Gonzalez, F., and Wahli, W., The PPARa - leukotriene B4 pathway to inflammation control, Nature, 1996; 384: 39–43.
  • Forman, B., Chen, J., and Evans, R., Hypo-lipidemic drugs, polyunsaturated fatty acids and eicosanoids are ligands for peroxisome proliferator-activated receptors a and d, Proc. Natl. Acad. Sci. (USA), 1997; 94: 4312–4317.
  • Sher, T., Yi, H. McBride, O. and Gonzalez, F., cDNA cloning, chromosomal mapping and functional characterization of the human per-oxisome proliferator activated receptor, Biochemistry, 1993; 32: 5598–5604.
  • Mukherjee, R., Jow, L., Noonan, D., and McDonnell, D., Human and rat peroxisome proliferator activated receptor (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAr activators, J. Steroid Mol. Biol., 1994; 51: 157–166.
  • Greene, M., Blumberg, B., McBride, O., Yi, H., Kronquist, K., Kwan, K., Hsieh, L., Greene, G., and Nimer, S., Isolation of the human per-oxisome proliferator activated receptor gamma cDNA: expression in hematopoitic cells and chromosomal mapping, Gene Exp., 1995; 4: 281–200.
  • Thottassery, J., Winberg, L., Youssef, J., Cunningham, M., and Badr, M., Regulation of perfluorooctanoic acid-induced peroxiso-mal activities and hepatocellular growth by adrenal hormones, Hepatology, 1992; 15: 316– 322.
  • Gray, R. and De la Iglesia, F., Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibro-zil in several species, Hepatology, 1984; 4: 520–530.
  • Reddy, J. and Lalwani, N., Carcinogenesis by hepatic peroxisome proliferators: Evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans, CRC Crit. Rev. Tox-icol. 1983; 12: 1–58.
  • Veitch, K. and Van Hoof, F., In vitro effects of eight-carbon fatty acids on oxidation in rat liver mitochondria, Biochem. Pharmacol., 1990; 40: 2153–2159.
  • Draye, J. and Vamecy, J. The inhibition by valproic acid of the mitochondrial oxidation of monocarboxylic and w-hydroxy monocarbox-ylic acids: possible implications for the metabolism of gamma-aminobutyric acid, J. Bio-chem., 1987; 102: 235–242.
  • Inouye, B., Ogino, Y., Ishida, T., Ogata, M., and Utsumi, K., Effects of phthalate esters on mitochondrial oxidative phosphorylation in the rat, Toxicol. Appl. Pharmacol., 1978; 43: 189– 198.
  • Keller, B., Yamanaka, H., and Thurman, R., Inhibition of mitochondrial respiration and oxygen-dependent hepatotoxicity by six structurally dissimilar peroxisomal proliferating agents, Toxicology, 1992; 71: 49–61.
  • Keller, B., Liang, D., and Thurman, R., 2-Ethylhexanol uncouples oxidative phosphory-lation in rat liver mitochondria, Toxicol. Lett., 1991; 57: 113–120.
  • Keller, B., Bradford, B., Marsman, D., Cattley, R., Popp, J., Bojes, H., and Thurman, R., The nongenotoxic hepatocarcinogen WY-14,643 is an uncoupler of oxidative phosphorylation in vivo, Toxicol. Appl. Pharmacol., 1993; 119: 52–58.
  • Melnick, R. and Schiller, C., Effect of phtha-late esters on energy coupling and succinate oxidation in rat liver mitochondria, Toxicology, 1985; 34: 13–27.
  • Takahashi, T., Biochemical studies on phthalic esters. II. Effects of phthalic acid esters on mi-tochondrial respiration of rat liver mitochondria, Biochem. Pharmacol., 1977; 26: 19–24.
  • Ohyama, T., Effects of phthalate esters on the respiration of rat liver mitochondria, J. Bio-chem., 1976; 79: 153–158.
  • Elcombe, C. and Mitchell, A., Peroxisome proliferation due to di(2-ethylhexyl) phtha-late (DEHP): species differences and possible mechanisms, Environ. Health Perspect., 1986; 70: 211–219.
  • Lake, B., Gangolli, S., Grasso, P., and Lloyd, A., Studies on the hepatic effects of orally administered di-(2-ethylhexyl) phthalate in the rat, Toxicol. Appl. Pharmacol., 1975; 32: 355–367.
  • Winberg, L. and Badr, M., Mechanism of ph-thalate-induced inhibition of hepatic mitochon-drial b-oxidation, Toxicol. Lett., 1995; 76: 63–69.
  • Katyal, S., Saha J., and Kabara, J., Effect in vitro of clofibrate and trans -1,4-bis-(2+chloro-benzylaminoethyl) -cyclohexane dihydrochlo-ride (AY 9944) on respiration and adenosine triphosphatase activity of mouse liver mitochondria, Biochem. Pharmacol., 1972; 21: 747–751.
  • Bereznowski, Z., Effect of methyl methacry-late on mitochondrial function and structure, Int J. Biochem., 1994; 26: 1119–1127.
  • Deschamps, D., DeBeco, V., Fisch, C., Fromenty, B., Guillouzo A., and Pessayre, D., Inhibition by perhexiline of oxidative phosphorylation and the b-oxidation of fatty acids: possible role inpseudoalcoholic liver lesions, Hepatology, 1994; 19: 948–961.
  • Hovik, R., Osmundsen, H., Berge., R., Aarsland, A., Bergseth S., and Bremer, J., Effects of thia-substituted fatty acids on mitochondrial and peroxisomal b-oxidation. Studies in vivo and in vitro, Biochem J., 1990; 270: 167–173.
  • Hawkins, J., Jones, W., Bonner F., and Gibson G., The effect of peroxisome proliferators on microsomal and mitochondrial enzyme activities in the liver and kidney, Drug Metabolism Reviews, 1987; 18: 441–515.
  • Permadi, H., Lundgren, B., Andersson, K., Sundberg, C., and DePierre, J., Effect of per-fluoro fatty acids on peroxisome proliferation and mitochondrial size in mouse liver: dose and time factors and effect of chain length, Xenobiotica, 1993; 23: 761–77.
  • Kurup, C. K. R., Aithal, H. N., and Ramasarma, T., Increase in hepatic mitochondria on administration of ethyl a-p-chlorophenoxyisobuty-rate to the rat, Biochem. J., 1970; 116: 773– 779.
  • Lundgren, B., Bergstrand, A., Karlsson, K., and DePierre, J. W., Effects of dietary treatment with clofibrate, nafenopin or WY-14,643 on mitochondria and DNA in mouse liver, Bio-chim. Biophys. Acta, 1990; 1035: 132–138.
  • Hakkola, E., Hiltunen, J., and Autio-Harmainen, H., Mitochondrial 2,4-dienoyl-CoA reductases in the rat: differential responses to clofibrate treatment, J. Lipid Res., 1994; 35: 1820–1828.
  • Svensson, L., Alexson, S., and Hiltunen, J., Very long chain and long chain acyl-CoA thi-oesterases in rat liver mitochondria. Identification, purification, charaterization, and induction by peroxisome proliferators, J. Biol. Chem., 1995; 270: 12177–1218.
  • Ganning, A., Olsson, M., Peterson, E., and Dallner, G., Fatty acid oxidation in hepatic per-oxisomes and mitochondria after treatment of rats with di(2-ethylhexyl) phthalate, Pharmacol. Toxicol., 1989; 65: 265–268.
  • Shindo, Y., Osumi, T., and Hashimoto, T., Effect of administration of di-(2-ethylhexyl) phthalate on rat liver mitochondria, Biochem. Pharmacol., 1978; 27: 2683–2688.
  • Lipsky, N. and Pedersen, P., Perturbation by clofibrate of mitochondrial levels in animal cells. Implications for a model of mitochondri-al genesis, J. Biol. Chem., 1982; 257: 1473– 1481.
  • Cederbaum, A., Madharan, T., and Rubin, E., Effect of chronic clofibrate administration on mitochondrial fatty acid oxidation, Biochem. Pharmacol., 1976; 25: 1285–1292.
  • Foxworthy, P. and Eacho, P., Effect of the per-oxisome proliferator LY 171883 on triglyceride accumulation in rats fed a fat-free diet, Bio-chem. Pharmacol., 1991; 42: 1487–1491.
  • Badr, M., Handler, J., Whittaker, M., Kauffman, F., and Thurman, R., Interactions between plas-ticizers and fatty acid metabolism in the perfused rat liver and in vivo: Inhibition of ketogen-esis by 2-ethylhexanol, Biochem. Pharmacol., 1990; 39: 715–721.
  • Berge, R., Aarsland, A., Kryvi, K., Bremer, J., and Aarsaeher, N., Alkylthio acetic acids (3-thia fatty acids) — A new group of non-b-oxidizable peroxisome-inducing fatty acid analogues. II. Dose-response studies on hepatic peroxisomal- and mitochondrial changes and long-chain fatty acid metabolizing enzymes in rats, Biochem Pharmacol., 1989; 38: 3969–3979.
  • Lake, B., Gray, T., Foster, J., Stubberfield, C., and Gangolli, S., Comparative studies on di-(2-ethylhexyl) phthalate-induced hepatic per-oxisome proliferation in the rat and hamster, Toxicol. Appl. Pharmacol., 1984; 72: 46–60.
  • Pacot, C., Chrmoillaux, M., Goudonnet, H., Truchot, R., and Latruffe, N., Role of thyroid state on induction by ciprofibrate of laurate hy-droxylase and peroxisomal enzymes in rat liver microsomes, Biochem. Pharmacol., 1993; 45: 1437–1446.
  • Cai, Y., Sohlenius, A-K., Andersson, K., Sundberg, C., and DePierre, J., Effects of acetyl-salicylic acid on parameters related to peroxi-some proliferation in mouse liver, Biochem. Pharmacol., 1994; 47: 2213–2219.
  • Rodriguez, J., Gil-Gomz, G., Hegardt, F., and Haro, D., Peroxisome proliferator-activated receptor mediates induction of the mitochondri-al 3-hydroxy-3-methylglutaryl-CoA synthe-tase gene by fatty acids, J. Biol. Chem., 1994; 269: 18767–18772.
  • Gulick, T., Cresci, S., Caira, T., Moore, D., and Kelly, D., The peroxisome proliferator receptor regulates mitochondrial fatty acid oxidative enzyme gene expression, Proc. Natl. Acad. Sci. (USA), 1994; 91: 11012–11016.
  • Chandoga, J., Hampl, L., Turecky, L., Rojekova, I., Uhlikova, E., and Hocman, G., Cetaben is an exceptional type of peroxisome proliferator, Int. J. Biochem., 1994; 26: 679– 696.
  • Chandoga, J., Rojekova, I., Hampl, L., and Hocman, G., Cetaben and fibrates both influence the activities of peroxisomal enzymes in different ways, Biochem. Pharmacol., 1994; 47: 515–519.
  • Lock, E., Mitchell, A., and Elcombe, C., Biochemical mechanisms of induction of hepatic peroxisome proliferation, Ann. Rev. Pharmacol. Toxicol., 1989; 29: 145–165.
  • Gibson, G., Comparative aspects of the mammalian cytochrome P450IV gene family, Xenobiotica, 1989; 19: 1123–1148.
  • Gibson, G. and Lake, B., Induction protocols for the cytochrome P450A subfamily in animals and primary hepatocyte cultures, Meth. Enzymol., 1991; 206: 353–364.
  • Anthony, L., Shmucker, D., Mooney, J., and Jones, A., A qualitative analysis of fine structure and drug metabolism in livers of clofibrate-treated young adult and retired breeder rats, J. Lipid Res., 1978; 19: 154–165.
  • Salvador, R., Haber, S., Atkins, C., Gommi, B., and Welch, R., The effect of clofibrate and 1-methyl-4-piperidyl-bis (p-chlorophe-noxy) acetate (Sandoz 43-348) on steroid and drug metabolism by rat liver microsomes, Life Sci., 1970; 9: 397–407.
  • Reich, N. and Ortiz de Montellano, P., Dissociation of increased lauric acid w-hydroxylase activity from the antilipidemic action of clofi-brate, Biochem. Pharmacol., 1987; 35: 1227– 1233.
  • Agarwal, D., Agarwal, S., and Seth, P., Effects of di-(2-ethylhexyl)phthalate on drug metabolism, lipid peroxidation, and sulfhyryl content of rat liver, Drug Metab. Dispos., 1982; 10: 77–80.
  • Diaz, M., Chinje, E., Kentish, P., Jarnot, B., George, M., and Gibson, G., Induction of cy-tochrome P450A by the peroxisome prolifera-tor perfluoro-n-octanoic acid, Toxicology, 1994; 86: 109–122.
  • 5. Nelson, D., Kamataki, T., Waxman, D., Guengerich, P., Estabrook, R., Feyereisen, R., Gonzalez, F., Coon, M., Gunsalus, I., Goton, O., Okuda, K., and Nebert, D., The P450 superfamily: update of new sequences, gene mapping, accession members, early trivial names of enzymes and nomenclature, DNA Cell Biol., 1993; 12: 1– 51.
  • Gibson, G., Orton, T., and Tamburini, P., Cy-tochrome P-450 induction by clofibrate, Bio-chem J., 1982; 203: 161–168.
  • Milton, M., Elcombe, C., and Gibson, G., On the mechanism of induction of microsomal cy-tochrome P450IVA1 and peroxisome proliferation in rat liver by clofibrate, Biochem. Pharmacol., 1990; 40: 2727–2732.
  • Orton, T. and Parker, G., The effect of hypo-lipidaemic drugs on the hepatic microsomal drug metabolizing enzyme system of the rat: induction of cytochrome(s) P-450 with specificity toward terminal hydroxylation of lauric acid, Drug Metab. Dispos., 1982; 10: 110–115.
  • Wortelboer, H., De Kruit, C., Van Iersel, A., Falke, H., Noordhoek, J., and Blaauboor, B., The isoenzyme pattern of cytochrome P-450 in rat hepatocytes in primary culture, comparing different incubations and in intact mono-layers, Biochem. Pharmacol., 1990; 40: 2525– 2534.
  • Sharma, R., Lake, B., and Gibson, G., Co-induction of microsomal cytochrome P-452 and the peroxisomal fatty acid b-oxidation pathway in the rat by clofibrate and di-(2-ethyl-hexyl)phthalate. Dose-response studies, Bio-chem. Pharmacol., 1988; 37: 1203–1206.
  • Bell, D., Bars, R., Gibson, G., and Elcombe C., Localization and differential induction of cytochrome P450IVA and acyl-CoA oxidase in rat liver, Biochem. J., 1991; 275: 247–252.
  • Chinje, E., Kentish, P., Jarnot, B., George, M., and Gibson, G., Induction of the CYP4A subfamily by perfluorooctanoic acid: the rat and the guinea pig as susceptible and non-susceptible species, Toxicol. Lett., 1994; 71: 69– 75.
  • Hardwick, J., Song, B., Huberman, E., and Gonzalez, F., Isolation, complementry DNA sequence and regulation of rat hepatic lauric acid w-hydroxylase (cytochrome P450 LAw). Identification of a new cytochrome P450 gene family, J. Biol. Chem., 1987; 262: 801–810.
  • Webb, S., Xiao, G-H., Geoghegan, T., and Prough, R., Regulation of CYP4A expression in rat by dehydroepiandrosterone and thyroid hormone, Mol. Pharmacol., 1996; 49: 276–287.
  • Sohlenius, A., Anderson, K., and DePierre, J., The effect of perfluoro-octanoic acid on hepatic peroxisome proliferation and related parameters show no sex-related differences in mice, Biochem. J., 1992; 285: 779–783.
  • Swinney, D., Webb, A., and Freedman, R., A novel rat hepatic clofibrate-inducible cytochrome P-450 that is not a lauric acid hydroxylase, Bio-chem. Pharmacol., 1991; 42: 2341–2349.
  • Hosokawa, M., Maki, T., and Satoh, T., Differences in the induction of carboxylesterase isozymes in rat liver microsomes by xenobi-otics, Biochem. Pharmacol., 1988; 37: 2708– 2711.
  • Hosokawa, M. and Satoh, T., Differences in the induction of carboxylesterase isozymes in rat liver microsomes by perfluorinated fatty acids, Xenobiotica, 1993; 23: 1125–1133.
  • Hosokawa, M., Hirata, K., Nakata, F., Suga, T., and Satoh, T., Species differences in the induction of hepatic microsomal carboxyles-terases caused by dietary exposure to di(2-ethyl-hexyl)phthalate, a peroxisome proliferator, Drug Metab. Dispos., 1994; 22: 889–894.
  • Schladt, L., Hartmann, R., Timms, C., Strolin-Benedetti, M., Dostert, P., Worner, W., and Oesch, F., Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal b-oxidation by various hypolipi-demic compounds, Biochem. Pharmacol., 1987; 36: 345–351.
  • Helmut, T., Schladt, L., Knehr, M., Post, K., Oesch, F., Boitenx-Antoine, A., Fournel-Gigleux, S., Madalou, J., and Siest, G., Effect of hypolipidemic compounds on lauric acid hy-droxylation and phase II enzymes, Biochem. Pharmacol., 1989; 38: 1963–1969.
  • Visser, T., Kaptein, E., and Harpur, E., Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischerrats, Biochem. Pharmacol., 1991; 42: 444– 446.
  • Barter, R. and Klaassen, C., Rat liver micro-somal UDP-glucuronosyltransferase activity toward thyroxine: Characterization, induction and form specificity, Toxicol. Appl. Pharmacol., 1992; 115: 261–267.
  • Manautou, J., Tveit, A., Hoivik, D., Khairallah, E., and Cohen, S., Protection by clofibrate against acetaminophen hepatotoxicity in male CD-1 mice is associated with an early increase in biliary concentration of acetaminophen-glu-tathione adducts, Toxicol. Appl. Pharmacol., 1996; 140: 30–38.
  • Furukawa, K., Numoto, S., Furuya, K., Furukawa, N., and Williams, G., Effects of the hepatocarcinogen nafenopin, a peroxisome pro-liferator, on the activities of rat liver glutath-ione-requiring enzymes and catalase in comparison to the action of phenobarbital, Cancer Res., 1985; 54: 5011–5019.
  • Satoh, A., Ogata, K., Ogata, Y., and Kato, N., Decreased activity of xanthine oxidase in rat liver by feeding with di-(2-ethylhexyl) phtha-late and clofibrate, Agric. Biol. Chem., 1990; 54: 2745–2746.
  • Foliot, A., Touchard, D., and Mallet, L., Inhibition of liver glutathione-S-transferase activity in rats by hypolipidemic drugs related or unrelated to clofibrate, Biochem. Pharmacol., 1986; 35: 1685–1690.
  • Foliot, A. and Beaune, P., Effects of microso-mal enzyme inducers on glutathione-S-trans-ferase isozymes in livers of rats and hamsters, Biochem. Pharmacol., 1994; 48: 293–300.
  • Moody, D., Loury, D., and Hammock, B., Epoxide metabolism in the liver of mice treated with clofibrate (ethyl-a-(p-chlorophenoxy-isobutyrate), a peroxisome proliferator, Toxi-col. Appl. Pharmacol., 1985; 78: 351–362.
  • Cai, Y., Appelkvist, E., and DePierre, J., Hepatic oxidative stress and related defenses during treatment of mice with acetylsalicylic acid and other peroxisome proliferators, J. Bio-chem. Toxicol., 1995; 10: 87–94.
  • Conway, J., Tomaszewski, K., Olson, M., Cattley, R., Marsman, D., and Popp, J., Relationship of oxidative damage to the hepatocar-cinogenecity of the peroxisome proliferatorsdi(2-ethylhexyl) phthalate and WY14,643, Car-cinogenesis, 1989; 10: 513–519.
  • Witzmann, F., Coughrie, M., Fultz, C., and Lipscomb, J., Effect of structurally diverse per-oxisome proliferators on rat hepatic sulfotrans-ferase, Chemico-Biological Interactions, 1996; 99: 73–84.
  • Kawai, Y., Takahashi, S., Satoh, A., and Kato, N., Decreased activity of xanthine dehydrogen-ase and serum uric acid in rats fed partially hydro-genated fish oil, Nutr. Res., 1993; 13: 1325– 1330.
  • Kelling, C., Van Rafelghem, M., Menahan, L., and Peterson, R., Effects of perfluorodecanoic acid on hepatic indices of thyroid status in the rat, Biochem. Pharmacol., 1987; 36: 1337–1344.
  • Lehotay, D., Gindler, J., and Paul, H., Effects of clofibrate on malic enzymes and phos-phodiesterase activities, Horm. Metabol. Res., 1987; 19: 663–664.
  • Badr, M., Induction of peroxisomal enzyme activities by di-(2-ethylhexyl) phthalate in thy-roidectomized rats with parathyroid replants, J. Pharmacol. Exp. Ther., 1992; 263: 1105– 1110.
  • Hertz, R., Aurbach, R., Hashimoto, T., and Bar-Tana, J., Thyromimetic effect of peroxi-somal proliferators in rat liver, Biochem. J., 1991; 274: 745–751.
  • Gastelein, H., Gulick, T., Declercq, P., Mannaerts, G., Moore, D., and Baes, M., The peroxisome proliferator activated receptor regulates malic enzyme gene expression, J. Biol. Chem., 1994; 269: 26754–26758.
  • Chu, R., Madison, L., Lin, Y., Kopp, P., Rao, M., Jameson, J. L., and Reddy, J., Thyroid hormone (T3) inhibits ciprofibrate-induced transcription of genes encoding b-oxidation enzymes: Cross-talk between peroxisome pro-liferator and T3 signaling pathways, Peroxi-somes: Biology and Role in Toxicology and Disease, an International Symposium, Aspen, CO, 1995; 49.
  • Su, C. and Lardy, H., Induction of hepatic mitochondrial glycerophosphate dehydrogen-ase in rats by dehydroepiandrosterone, J. Bio-chem., 1991; 110: 207–213.
  • Song, M., Grieco, D., Rall, J., and Nikodem, V., Thyroid hormone mediated transcriptional activation of the rat liver malic enzyme gene by dehydoepiandrosterone, J. Biol. Chem., 1989; 264: 18981–18985.
  • Zelewski, M. and Swierczynski, J., Clofibrate feeding increases cytoplasmic but not mitochon-drial malic enzyme activity in rat kidney cortex, Cell Biochem. Function, 1989; 7: 97–103.
  • Olson, C. and Anderson, M., The acute toxic-ity of perfluorodecanoic acid in male rats and effects on tissue fatty acids, Toxicol. Appl. Pharmacol., 1983; 70: 362–372.
  • Borges, T., Glauert, H., Chen, L., Chen, C., and Robertson, L., Effect of the peroxisome proliferator perfluorodecanoic acid on growth and lipid metabolism in Sprauge-Dawley rats fed three dietary levels of selenium, Arch. Tox-icol., 1990; 64: 26–30.
  • Zelewski, M. and Swierczynski, J., The effect of clofibrate feeding on the NADP-dehydro-genases activity in rat tissue, Biochim. Biophys. Acta, 1983; 758: 152–157.
  • Zelewski, M. and Swierczynski, J., The influence of prolonged clofibrate treatment on the plasma drug concentration and liver NADP-linked enzymes activity, Gen. Pharmacol., 1986; 17: 117–119.
  • Shackleton, G., Gibson, G., Sharma, R., Howes, D., Orrenius, S., and Kass, G., Diverse mechanisms of calcium mobilization by peroxisome proliferators in rat hepatocytes, Toxicol. Appl. Pharmacol., 1995; 130: 294–303.
  • Ochsner, M., Creba, J., Bentley, P., and Mukkassah-Kelly, S., Nafenopin, a hypolip-idemic and non-genotoxic hepatocarcinogen increases intracellular calcium and transiently decreases intracellular pH in hepatocytes without generation of inositol phosphates, Biochem. Pharmacol., 1990; 40: 2247–2257.
  • Bennett, A. and Williams, G., Reduction in rat liver endoplasmic reticulum Ca2+ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome prolifer-ator, Biochem. Pharmacol., 1992; 43: 595–605.
  • Bennett, A. and Williams, G., Alteration of rat liver endoplasmic reticulum Ca2+-ATPase thiol integrity by ciprofibrate, a peroxisome proliferator, Biochem Pharmacol., 1993; 45: 2093–2098.
  • Vac, N., Schoonjans, K., Kosykh, V., Dallongeville, J., Fruchart, J-C., Staels, B., and Auwerx, J., Fibrates increase human apoli-poprotein A-II expression through activation of the peroxisome proliferator-activated receptor, J. Clin. Invest., 1995; 96: 741–750.
  • Nicholls-Grzemski, F., Calder, I., and Priestly, B., Peroxisome proliferators protect against paracetamol hepatotoxicity in mice, Biochem. Pharmacol., 1992; 43: 1395–1396.
  • Manautou, J., Hoivik, D., Tveit, A., Hart, S., Khairallah, E., and Cohen, S., Clofibrate pretreatment diminishes acetaminophen’s selective covalent binding and hepatotoxicity, Tox-icol. Appl. Pharmacol., 1994; 129: 252–263.
  • Sohlenius, A., Eriksson, A., Kimland, M., and DePierre, J., Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid b-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver, Pharmacol. Toxicol., 1993; 72: 90–93.
  • Motojima, K., Ohmori, A., Takino, Y., and Goto, S., Increase in the amount of elongation factor 2 in rat liver by peroxisome prolifera-tors, J. Biochem., 1993; 114: 779–785.
  • Kobayashi, T., Shimizugawa, T., Fukamizu, Y., Huang, M-Z., Watanabe S., and Okuyama, H., Assessment of the possible adverse effects of oils enriched with n-3 fatty acids in rats; per-oxisomal proliferation, mitochondrial dysfunctions and apoplexy, J. Nutr. Biochem., 1996; 7: 542–548.
  • Ishii, H., Horie, S., and Suga, T., Physiological role of peroxisomal b-oxidation in liver of fasted rats, J. Biochem., 1980; 87: 1855–1858.
  • Irizar, A. and Ioannides, C., Extrahepatic expression of P450 proteins in insulin-dependent diabetes mellitus, Xenobiotica, 1995; 25: 941– 949.
  • Shimojo, N., Ishizaki, T., Imaoka, S., Funae, Y., Fujiin, S., and Okuda, K., Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes, Biochem. Pharmacol., 1993; 46: 621– 627.
  • Barnett, C., Gibson, G., Wolf, C., Flatt, P., and Ioannides, C., Induction of cytochrome P450 III and P450 IV family proteins in streptozo-tocin-induced diabetes, Biochem. J., 1990; 268: 765–769.
  • Zanger, R. and Novak, R. F., Effects of fatty acids and ketone bodies on cytochromes P450 2B, 4A and 2E1 expression in primary cultured rat hepatocytes, Arch. Biochem Biophys., 1997; 337: 217–224.
  • Okorodudu, A., Adegboyega, P., and Scholz, C., Intracellular calcium and hydrogen ions in diabetes mellitus, Ann. Clin. Lab. Sci., 1995; 25: 394–401.
  • Hummerich, H. and Soboll, S., Rapid stimulation of calcium uptake into rat liver by L-tri-iodothyronine, Biochem. J., 1989; 258: 363– 367.
  • Pollera, M., Locci-Cubeddu, T., and Bergamini, E., Effect of cold adaptation on liver peroxi-somes and peroxisomal oxidative activities of rat: a morphometric/stereologic and biochemical study, Intern. Physiol. Biochim., 1983; 91: 35–42.
  • Koza, R., Kozak, U., Brown, L., Leiter, E., MacDonald, M., and Kozak, L., Sequence and tissue-dependent RNA expression of mouse FAD-linked glycerol-3-phosphate dehydrogenase, Arch. Biochem. Biophys., 1996; 336: 97–104.
  • Shmerling, M. and Filiushina, E., The ultrastructural of hepatocytes during the adaptation of rats to cold, Morphologiia, 1993; 105: 90– 97.
  • Iossa, S., Barletta, A., and Liverini, G., Different effects of cold exposure and cold acclimation on rat liver mitochondrial fatty acid oxidation and ketone bodies production, Inter. J. Biochem., 1994; 26: 425–431.
  • Stott, W., Chemically induced proliferation of peroxisome: implications for risk assessment, Regulatory Toxicol. Pharmacol., 1988; 8: 125– 159.
  • Huber, W. A. H., Grasl-Kraupp, B., and Schulte-Hermann, R., Hepatocarcinogenic potential of di(2-ethylhexyl) phthalate in rodents and its implications on human risk, CRC Crit Rev Tox-icol., 1996; 26: 365–481.
  • Reddy, J., Azarnoff, D., and Hignite, C., Hypo-lipidemic hepatic peroxisome proliferators form a novel class of chemical carcinogens, Nature, 1980; 283: 397–398.
  • Kraupp-Grassl, B., Huber, W. A. H., Taper, H., and Schulte-Hermann, R., Increased susceptibility of aged rats to hepatocarcinogenesis by the peroxisome proliferator nafenopin and the possible involvement of altered liver foci occuring spontaneously, Cancer Res., 1991; 51: 666–671.
  • Soliman, M., Cunningham, M., Morrow, J., Roberts, L. J., II, and Badr, M., Evidence against peroxisome proliferation-induced hepatic oxida-tive damage: Levels of esterified isoprostanes in livers of mice fed a diet containing [4-chloro-6(2,3 xylidino) - 2- pyrimidinylthio] acetic acid (WY-14,643), Biochem. Pharmacol., 1997; 53: 1369–1374.
  • Conway, J. and Popp, J., Effect of the hepato-carcinogenic peroxisome proliferator WY-14,643 in vivo: no increase in ethane exhalation or hepatic cojugated dienes, Toxicol. Appl. Pharmacol., 1995; 135: 229–236.
  • Pineau, T., Hudgins, W. R., Liu, L., Chen, L., Sher, T., Gonzalez, F., and Samid, D. Activation of a human peroxisome proliferator-acti-vated receptor by the antitumor agent phenyl-acetate and its analogs, Biochem. Pharmacol., 1996; 52: 659–667.
  • Hanefeld, M., Kemmer, C., and Kadner, E., Relationship between morphological changes and lipid-lowering action of p-chlorphenoxy-isobutyric acid (CPIB) on hepatic mitochondria and peroxisomes in man, Atherosclerosis, 1983; 46: 239–246.
  • IARC monographs on the evaluation of carcinogenic risks to humans, some pharmaceutical drugs, 1996; 66: 391–444.
  • Niort, G., Gambino, R., Cassader, M., and Pagano, G., Bezafibrate affects lipid,lipo- and apolipoprotein pattern in non-insulin-dependent diabetic patients, Horm. Metab. Res., 1993; 25: 372–374.
  • Newman, T. and Hulley, S., Carcinogenicity of lipid-lowering drugs, J. Am. Med. Assoc., 1996; 275: 55–60.
  • Levy, G., Clinical pharmacokinetics of aspirin, Pediatrics, 1978; 62(Suppl): 867–872.
  • Wientjes, M. G. and Levy, G., Nonlinear phar-macokinetics of aspirin in rats, J. Pharmacol. Exp. Ther., 1988; 245: 809–815.
  • Nelson, E., Hanano, M., and Levy, G., Comparative pharmacokinetics of salicylate elimination in man and rats, J. Pharmacol. Exp. Ther., 1966; 153: 159–166.
  • Morris, M., Pharmacokinetics and protein binding of salicylate metabolites in rats, Drug Metab. Dispos., 1990; 18: 809–811.
  • Owen, M. and Halestrap, A., The mechanism by which mild respiratory chain inhibitors inhibit hepatic gluconeogenesis, Biochem. Bio-phys. Acta, 1993; 1142: 11–22.
  • Bojes, H., Sausen, P., Cattley, R., Keller, B., and Thurman, R., Paradoxical increase in per-oxisomal cyanide-insensitive respiration following dietary exposure to WY-14,643 in the perfused liver, Toxicol. Appl. Pharmacol., 1996; 137: 202–209.
  • Mousseau, D. and Butterworth, R., Current theories on the pathogenesis of hepatic enceph-alopathy, Proc. Soc. Exp. Biol. Med., 1994; 206: 329–344.
  • Glick, B. and Rothman, J., Possible role for fatty acyl-coenzyme A in intracellular protein transport, Nature, 1987; 326: 309–312.
  • King, M., Pugazhenthi, S., Khandelwal, R., and Sharma, R., Elevated N-myristoyl trans-ferase activity is reversed by sodium orthovan-adate in streptozotocin-induced diabetic rat, Bichem. Biophys. Acta, 1993; 1165: 259–262.
  • Buss, J., Kamp, M., and Sefton, B., Myristic acid is attached to the transforming protein of rous sarcoma virus during or immediately after synthesis and is present in both soluble and membrane-bound forms of the protein, Mol. Cell. Biol., 1984; 4: 2697–2704.
  • Pounds. J., The role of cell calcium in current approaches to toxicology, Environ. Health Per-spect., 1990; 84: 7–15.
  • Cheung, J., Bonaventure, J., Malis, C., and Leaf, A., Calcium and ischemic injury, N. Engl. J. Med., 1986; 314: 1670–1676.
  • Rasmussen, H., Barrett, P., Smallwood, J., Bollag, W., and Isales, C., Calcium ions as intracellular messenger and cellular toxin, Environ. Health Perspect., 1990; 84: 17–25.
  • Farber, J., The role of calcium ions in toxic cell injury, Environ. Health Perspect., 1990; 84: 107–111.
  • Thor, H., Hartzell, P., and Orrenius, S., Poten-tiation of oxidative cell injury in hepatocytes which have accumulated Ca2+, J. Biol. Chem., 1984; 259: 6612–6615.
  • Nishizuki, Y., Intracellular signaling by hydrolysis of phospholipids and protein kinase C, Science, 1992; 258: 607–614.
  • O’Malley, B., Schrader, W., Mani, S., Smith, C., Weigel, N., Conneely, O., and Clark, J., An alternative ligand-independent pathway for activation of steroid receptors, Recent Adv. Horm. Res., 1995; 50: 333–347.
  • Bojes, H. and Thurman, R., Peroxisome prolif-erators inhibit acyl-CoA synthetase and stimulate protein kinase C in vivo, Toxicol. Appl. Pharmacol., 1994; 126: 233–239.
  • Leibold, E., Greim, H., and Schawrz, L., Inhibition of intercellular communication of rat hepatocytes by nafenopin: involvement of protein kinase C, Carcinogenesis, 1994; 15: 1265– 1267.
  • Rokos, C. and Ledwith, B., Peroxisome prolif-erators activate extracellular signal-regulated kinases in immortalized mouse liver cells, J. Biol. Chem., 1997; 272: 13452–13457.
  • Bond, J. and Butler, P. E., Intracellular proteases, Annu. Rev. Biochem., 1987; 56: 333– 364.
  • Goldstein, D., Feistner, G., Faull, K., and Tower, K., Plasticizers as contaminants in commercial ethanol, Alcoholism: Clin. Exp. Res., 1987; 11: 521–524.
  • Kaptein, E., Thyroid hormone metabolism and thyroid diseases in chronic renal failure, Endocrine Rev., 1996; 17:45–63.
  • Cohn, J., Ingbar, S., and Braverman, L., Thy-rotoxicosis due to ingestion of excess thyroid hormone, Endocrine Rev., 1989; 10: 113–124.
  • Cayen, M., Disposition, metabolism and phar-macokinetics of antihyperlipidemic agents in laboratory animals and man, Pharmacol. Ther., 1985; 29: 157–204.
  • Worrell, N., Cook, W., Thompson, C., and Gray, T., Effect of mono-(2-ethylhexyl) phthalate on the metabolism of energy yielding substrates in rat Sertoli cell-enriched cultures, Toxicol. In Vitro, 1989; 3: 77–81.
  • Agarwal, D., Eustis, S., Lamb, C., and Kluwe, W., Influence of dietary zinc on di(2-ethyl-hexyl) phthalate-induced testicular atrophy and zinc depletion in adult rats, Toxicol. Appl. Pharmacol., 1986; 84: 12–24.
  • Chu, I., Poom, R., Lecavalier, P., Mueller, R., Valli, V., and Procter, B., Subchronic oral toxicity of di-n-octylphthalate(DNOP) and di-(2-ethyl hexyl) phthalate (DEHP) in the rat, Toxicologist, 1995; 15: 1278.
  • Liu, R., Hahn, C., and Hutt, M., The direct effect of 11 hepatic peroxisome proliferators (PPs) on rat Leydig cell function in vitro, Tox-icologist, 1995; 15: 1291.
  • Eagon, P., Chander, N., Epley, M., Elm, M., Brady, E., and Rao, K., Di(2-ethylhexyl)phthal-ate-induced changes in liver estrogen metabolism and hyperplasia. Int. J. Cancer, 1994; 58: 736–743.
  • Eagon, P., M., Elm, Epley, M., Schinozuka, H., and Rao, K., Peroxisome proliferators: sex steroid receptors and metabolism in hepatic hyper-plasia and neoplasia, Toxicologist, 1996; 15: 1057.
  • Corton, J. C., Bocos, C., Moreno, E. S., Merritt, A., Marsman, D., Sausen, P., Cattley, R. and Gustafsson, J-A., Rat 17 b-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene, Mol. Pharmacol., 1996; 50: 1157–1166.
  • Corton, J. C., Bocos, C., Moreno, E. S., Merritt, A., Cattley, R. C., and Gustafsson, J-A., Perox-isome proliferators alter the expression of estrogen metabolizing enzymes, Biochimie, 1997; 79: 151–162.
  • Bahadur, G., Ling, K., and Katz, M., Statistical modeling reveals demography and time are the main contributing factors in global sperm count changes between 1938 and 1996, Human Rep., 1996; 11: 2635–2639.
  • Lamb, E. and Bennett, S., Epidemiological studies of male factors in infertility, Ann. N.Y. Acad. Sci., 1994; 709: 165–178.
  • Broustas, C., Larkins, L., Uhler, M., and Hajra, A., Molecular cloning and expression of cDNA encoding rat brain cytosolic acyl-coenzyme A thiester hydrolase, J. Biol. Chem., 1996; 271: 10470–10476.
  • Chandra, A. and Mosher, W., The demography of infertility and the use of medical care for infertility, Infert. Rep. Med. Clin. North Am., 1994; 5: 283–296.
  • Sallmen, M., Lindbahm, M-L., Kyyronen, P., Nykyri, E., Anttila, A., Taskinen, H., and Hemminki, K., Reduced fertility among woman exposed to organic solvents, Am. J. Industr. Med., 1995; 27: 699–713.
  • Nathan, L. and Chaudhuri, G., Estrogens and atherosclerosis, Annu. Rev. Pharmacol. Tox-icol., 1997; 37: 477–515.
  • Riggs, L. and Melton, L. J., The prevention and treatment of osteoporosis, N. Engl. J. Med., 1992; 327: 620–627.
  • Mochizuki, Y., Furukaea, K., and Sawada, N., Effects of various concentrations of ethyl-a-p-chlorophenoxyisobutyrate (clofibrate) on diethyl-nitrosoamine-induced hepatic tumorigenesis in the rat, Carcinogenesis, 1982; 3: 1027–1029.
  • Voskoboinik, I., Drew, R. and Ahokas, J. T., Peroxisome proliferator nafinopin potentiated cytotoxicity and genotoxicity of cyclophospha-mide in the liver and bone marrow cells, Chem-ico. Biol. Inter., 1997; 105: 81–97.
  • Patrono, C., Aspirin as an antiplatelet drug, N. Engl. J. Med., 1994; 330: 1287–1294.
  • Baldessarin, R., Drugs and the treatment of psychiatric disorders. Depression and Mania. In: The Pharmacological Basis of Therapeutics (Hardman, J., Limbird, L., Molinoff, P., Ruddon, R., and Gilman, A., Eds.). McGraw-Hill, New York, 9th ed., 1996, 431–459.
  • Youssef, J. and Badr, M., Activated Kupffer cells attenuate the liver response to the peroxi-some proliferator perfluorooctanoic acid, Mol. Cell. Biochem., 1997; 169: 143–147.
  • Bojes, H. and Thurman, R., Peroxisome prolif-erators activate Kupffer cells in vivo, Cancer Res., 1996; 56: 1–4.
  • Smith, A., Francis, J., Walters, D., and Lake, B., Protection against iron-induced uroporphy-ria in C57BL/10ScSn mice by the peroxisome proliferator nafenopin, Biochem. Pharmacol., 1990; 40: 2564–2568.
  • Ikeda, T., Aiba, K., Fukuda, K., and Tanaka, M., The induction of peroxisome proliferation in rat liver by perfluorinated fatty acids, metabolically inert derivatives of fatty acids, J. Biochem., 1985; 98: 475–485.
  • Rao, M., Ide, B., Subarrao, V., and Reddy, J., Dehydroepiandrosterone-induced peroxisome proliferation in the rat: evaluation of sex differences, Proc. Soc. Exp. Biol. Med., 1994; 207: 186–190.
  • Yamada, J., Sakuma, M., Ikeda, T., Fukuda, K., and Suga, T., Characteristics of dehydroepi-androsterone as a peroxisome proliferator, Bio-chem. Biophys. Acta, 1991; 1092: 233–243.
  • Becker, C. and Harris, R., Influence of valproic acid on hepatic carbohydrate and lipid metabolism, Arch. Biochem. Biophys., 1983; 223: 381–392.

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