Extraperoxisomal targets of peroxisome proliferators: Mitochondrial, microsomal, and cytosolic effects. Implications for health and disease

Critical Reviews in Toxicology

Volumn 28, Issue 1, 1998, Pages 1-33

  Youssef, Jihan ^a   Badr, Mostafa ^a  

^a UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

Author keywords

Cytosol; Health risk; Microsomes; Mitochondria; Peroxisome proliferators

Indexed keywords

CARBOXYLIC ACID DERIVATIVE; FIBRIC ACID DERIVATIVE; PEROXISOME PROLIFERATOR; PHENOXYACETIC ACID DERIVATIVE; PHTHALIC ACID DERIVATIVE;

ENZYME INDUCTION; HEALTH HAZARD; HEPATOSPLENOMEGALY; HUMAN; MICROSOME; MITOCHONDRIAL RESPIRATION; NONHUMAN; PEROXISOME; REVIEW; TOXIN ANALYSIS;

ANIMALS; ANTILIPEMIC AGENTS; ANTINEOPLASTIC AGENTS; CARCINOGENS; CYTOSOL; ENZYME INDUCTION; FATTY ACIDS; FLUOROCARBONS; HEPATOMEGALY; HERBICIDES; LIVER; LIVER NEOPLASMS; MICE; MICROBODIES; MICROSOMES, LIVER; MITOCHONDRIA, LIVER; PLASTICIZERS; RATS;

ANIMALIA; RODENTIA;

EID: 0031911722     PISSN: 10408444     EISSN: None     Source Type: Journal    
DOI: 10.1080/10408449891344182     Document Type: Review

References (209)

1. Lazarow, P. and Fujiki, Y., Biogenesis of peroxisomes, Ann. Rev. Cell Biol., 1985; 1: 489-530.
2. 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.
3. Staubli, R., Hess, R., and Weibel, E., Correlated morphometric and biochemical studies on the rat liver cell. H. Effects of phenobarbital on rat hepatocytes, J. Cell. Biol., 1969; 42: 92-112.
4. 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 morphometric data for rat liver, J. Cell Biol., 1969; 42: 68-91.
5. Schutgens, R., Heyman, H., Wanders, R., Vandenbosch, H., and Tager, J. Peroxisomal disorders: A newly recognized group of genetic diseases, Eur. J. Pediatr., 1986; 144: 430-440.
6. Tolbert, N., Metabolic pathways in peroxisomes and glyxysomes, Ann. Rev. Biochem., 1981; 50: 133-157.
7. Xu, L., Ash, M., Abdel-aleem, S., Lowe, J., and Badr, M. Hyperinsulinemia inhibits hepatic peroxisomal β-oxidation in rats, Horm. Metab. Res., 1995; 27: 76-78.
8. Singh, I., Biochemistry of peroxisomes in health and disease, Mol. Cell. Biochem., 1997; 167: 1-29.
9. Paget, G., Experimental studies of the toxicity of atromid with particular reference to fine structural changes in the livers of rodents, J. Atheroscler. Res., 1963; 3: 729-736.
10. Oesch, F., Schladt, L., Steinberg, P., and Thomas, H. Concomitant induction of cytosolic epoxide hydrolase and peroxisomal β-oxidation by hypolipidemic compounds in rat and guinea pig liver, Arch. Toxicol., 1988; 12 (Suppl): 248-255.
11. Eacho, P., Foxworthy, P., Johnson, W., Hoover, D. and White, S. Hepatic peroxisomal changes induced by a tetrazole-substituted alkoxyacetophenone in rats and comparison with other species, Toxicol. Appl. Pharmacol., 1986; 83: 430-437.
12. 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.
13. Watanabe, T., Horie, S., Yamada, J., Isaji, M., Nishigaki, T., Naito J., and Suga, T., Species differences in the effect of bezafibrate, a hypolipidemic agent, on hepatic peroxisome-associated enzymes, Biochem. Pharmacol., 1989; 38: 367-371.
14. De la Iglesia, F., Lewis, J., Buchanan, R., Marcus E., and Mc Mahon, G., Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment, Atherosclerosis, 1982; 43: 19-37.
15. Sakuma, M., Yamada, J., and Suga, T., Comparison of the inducing effect of dehydroepiandrosterone on hepatic peroxisome proliferation-associated enzymes in several rodent species, Biochem. Pharmacol., 1992; 43: 1269-1273.
16. Bronfman, M., Amigo, L., and Morales, M., Activation of hypolipidaemic drugs to acyl-coenzyme A thioesters, Biochem J., 1986; 239: 781-784.
17. Hertz, R. and Bar-Tana, J., The acylation of proteins by xenobiotic amphipathic carboxylic acid in cultured rat hepatocytes, Biochem. J., 1988; 254: 39-44.
18. 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.
19. 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.
20. 2+-channel blockers, Biochem. J., 1994; 301: 753-758.
21. Horie, S., Ishii, H., and Suga, T., Changes in pcroxisomal fatty acid oxidation in the diabetic rat liver, J. Biochem., 1981; 90: 1691-1696.
22. Thomas, H., Schladt, L., Knehr M., and Oesch, F., Effect of diabetes and starvation on the activity of rat liver epoxide hydrolase, glutathione-S-transferase and peroxisomal β-oxidation, Biochem. Pharmacol., 1989; 38: 4291-4297.
23. Fringes, B. and Reith, A., Time-course of peroxisome biogenesis during adaptation to mild hyperthyroidism in rat liver, Lab. Invest., 1982; 47: 19-26.
24. Fringes, B., Reith, A., and Riede, U., Peroxisome biogenesis in rat liver during adaptation to mild hyperthyroidism: a morphometric/stereologic study by electron microscopy, Ann. N. Y. Acad. Sci. (USA), 1982; 386: 514-518.
25. Levy, E., Slusser, R., and Ruebner, B., Hepatic changes produced by a single dose of endotoxin in the mouse, Am. J. Path., 1968; 52: 477-502.
26. Neat, C., Thomassen, M., and Osmundsen, H. Induction of peroxisomal β-oxidation in rat liver by a high-fat diet, Biochem. J., 1980; 186: 369-371.
27. Issemann, I. and Green, S., Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators, Nature, 1990; 347: 645-650.
28. Tsai, M. and O'Malley, B. Molecular mechanisms of action of steroid/thyroid receptor superfamily members, Ann. Rev. Biochem., 1994; 63: 451-486.
29. 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.
30. 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 proliferator-activated receptors, Proc. Natl. Acad. Sci. (USA), 1994; 91: 7344-7349.
31. 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 peroxisome proliferator-activated receptors α and γ, Proc. Natl. Acad. Sci. (USA), 1997; 94: 4318-4323.
32. 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 γ and the retinoid X receptor, Proc. Natl. Acad. Sci. (USA), 1997; 94: 237-241.
33. 4 pathway to inflammation control, Nature, 1996; 384: 39-43.
34. Forman, B., Chen, J., and Evans, R., Hypolipidemic drugs, polyunsaturated fatty acids and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ, Proc. Natl. Acad. Sci. (USA), 1997; 94: 4312-4317.
35. Sher, T., Yi, H. McBride, O. and Gonzalez, F., cDNA cloning, chromosomal mapping and functional characterization of the human peroxisome proliferator activated receptor, Biochemistry, 1993; 32: 5598-5604.
36. 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.
37. Greene, M., Blumberg, B., McBride, O., Yi, H., Kronquist, K., Kwan, K., Hsieh, L., Greene, G., and Nimer, S., Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoitic cells and chromosomal mapping, Gene Exp., 1995; 4: 281-200.
38. Thottassery, J., Winberg, L., Youssef, J., Cunningham, M., and Badr, M., Regulation of perfluorooctanoic acid-induced peroxisomal activities and hepatocellular growth by adrenal hormones, Hepatology, 1992; 15: 316-322.
39. Gray, R. and De la Iglesia, F., Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibrozil in several species, Hepatology, 1984; 4: 520-530.
40. 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. Toxicol. 1983; 12: 1-58.
41. 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.
42. Draye, J. and Vamecy, J. The inhibition by valproic acid of the mitochondrial oxidation of monocarboxylic and ω-hydroxy monocarboxylic acids: possible implications for the metabolism of gamma-aminobutyric acid, J. Biochem., 1987; 102: 235-242.
43. 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.
44. 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.
45. Keller, B., Liang, D., and Thurman, R., 2-Ethylhexanol uncouples oxidative phosphorylation in rat liver mitochondria, Toxicol. Lett., 1991; 57: 113-120.
46. 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.
47. Melnick, R. and Schiller, C., Effect of phthalate esters on energy coupling and succinate oxidation in rat liver mitochondria, Toxicology, 1985; 34: 13-27.
48. Takahashi, T., Biochemical studies on phthalic esters. II. Effects of phthalic acid esters on mitochondrial respiration of rat liver mitochondria, Biochem. Pharmacol., 1977; 26: 19-24.
49. Ohyama, T., Effects of phthalate esters on the respiration of rat liver mitochondria, J. Biochem., 1976; 79: 153-158.
50. Elcombe, C. and Mitchell, A., Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms, Environ. Health Perspect., 1986; 70: 211-219.
51. 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.
52. Winberg, L. and Badr, M., Mechanism of phthalate-induced inhibition of hepatic mitochondrial β-oxidation, Toxicol. Lett., 1995; 76: 63-69.
53. Katyal, S., Saha J., and Kabara, J., Effect in vitro of clofibrate and trans -1,4-bis-(2+chlorobenzylaminoethyl)-cyclohexane dihydrochloride (AY 9944) on respiration and adenosine triphosphatase activity of mouse liver mitochondria, Biochem. Pharmacol., 1972; 21: 747-751.
54. Bereznowski, Z., Effect of methyl methacrylate on mitochondrial function and structure, Int J. Biochem., 1994; 26: 1119-1127.
55. Deschamps, D., DeBeco, V., Fisch, C., Fromenty, B., Guillouzo A., and Pessayre, D., Inhibition by perhexiline of oxidative phosphorylation and the β-oxidation of fatty acids: possible role in pseudoalcoholic liver lesions, Hepatology, 1994; 19: 948-961.
56. Hovik, R., Osmundsen, H., Berge., R., Aarsland, A., Bergseth S., and Bremer, J., Effects of thiasubstituted fatty acids on mitochondrial and peroxisomal β-oxidation. Studies in vivo and in vitro, Biochem J., 1990; 270: 167-173.
57. 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.
58. Permadi, H., Lundgren, B., Andersson, K., Sundberg, C., and DePierre, J., Effect of perfluoro 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.
59. Kurup, C. K. R., Aithal, H. N., and Ramasarma, T., Increase in hepatic mitochondria on administration of ethyl α-p-chlorophenoxyisobutyrate to the rat, Biochem. J., 1970; 116: 773-779.
60. 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, Biochim. Biophys. Acta, 1990; 1035: 132-138.
61. 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.
62. Svensson, L., Alcxson, S., and Hiltunen, J., Very long chain and long chain acyl-CoA thioesterases in rat liver mitochondria. Identification, purification, charaterization, and induction by peroxisome proliferators, J. Biol. Chem., 1995; 270: 12177-1218.
63. Ganning, A., Olsson, M., Peterson, E., and Dallner, G., Fatty acid oxidation in hepatic peroxisomes and mitochondria after treatment of rats with di(2-ethylhexyl) phthalate, Pharmacol. Toxicol., 1989; 65: 265-268.
64. 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.
65. Lipsky, N. and Pedersen, P., Perturbation by clofibrate of mitochondrial levels in animal cells. Implications for a model of mitochondrial genesis, J. Biol. Chem., 1982; 257: 1473-1481.
66. Cederbaum, A., Madharan, T., and Rubin, E., Effect of chronic clofibrate administration on mitochondrial fatty acid oxidation, Biochem. Pharmacol., 1976; 25: 1285-1292.
67. Foxworthy, P. and Eacho, P., Effect of the peroxisome proliferator LY 171883 on triglyceride accumulation in rats fed a fat-free diet, Biochem. Pharmacol., 1991; 42: 1487-1491.
68. Badr, M., Handler, J., Whittaker, M., Kauffman, F., and Thurman, R., Interactions between plasticizers and fatty acid metabolism in the perfused rat liver and in vivo: Inhibition of ketogenesis by 2-ethylhexanol, Biochem. Pharmacol., 1990; 39: 715-721.
69. Berge, R., Aarsland, A., Kryvi, K., Bremer, J., and Aarsaeher, N., Alkylthio acetic acids (3-thia fatty acids) - A new group of non-β-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.
70. Lake, B., Gray, T., Foster, J., Stubberfield, C., and Gangolli, S., Comparative studies on di-(2-ethylhexyl) phthalate-induced hepatic peroxisome proliferation in the rat and hamster, Toxicol. Appl. Pharmacol., 1984; 72: 46-60.
71. Pacot, C., Chrmoillaux, M., Goudonnet, H., Truchot, R., and Latruffe, N., Role of thyroid state on induction by ciprofibrate of laurate hydroxylase and peroxisomal enzymes in rat liver microsomes, Biochem. Pharmacol., 1993; 45: 1437-1446.
72. Cai, Y., Sohlenius, A-K., Andersson, K., Sundberg, C., and DePierre, J., Effects of acetylsalicylic acid on parameters related to peroxisome proliferation in mouse liver, Biochem. Pharmacol., 1994; 47: 2213-2219.
73. Rodriguez, J., Gil-Gomz, G., Hegardt, F., and Haro, D., Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthetase gene by fatty acids, J. Biol. Chem., 1994; 269: 18767-18772.
74. 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.
75. 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.
76. 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.
77. Lock, E., Mitchell, A., and Elcombe, C., Biochemical mechanisms of induction of hepatic peroxisome proliferation, Ann. Rev. Pharmacol. Toxicol., 1989; 29: 145-165.
78. Gibson, G., Comparative aspects of the mammalian cytochrome P450IV gene family, Xenobiotica, 1989; 19: 1123-1148.
79. Gibson, G. and Lake, B., Induction protocols for the cytochrome P450A subfamily in animals and primary hepatocyte cultures, Meth. Enzymol., 1991; 206: 353-364.
80. 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.
81. Salvador, R., Haber, S., Atkins, C., Gommi, B., and Welch, R., The effect of clofibrate and 1-methyl-4-piperidyl-bis (p-chlorophenoxy) acetate (Sandoz 43-348) on steroid and drug metabolism by rat liver microsomes, Life Sci., 1970; 9: 397-407.
82. Reich, N. and Ortiz de Montellano, P., Dissociation of increased lauric acid ω-hydroxylase activity from the antilipidemic action of clofibrate, Biochem. Pharmacol., 1987; 35: 1227-1233.
83. 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.
84. Diaz, M., Chinje, E., Kentish, P., Jarnot, B., George, M., and Gibson, G., Induction of cytochrome P450A by the peroxisome proliferator perfluoro-n-octanoic acid, Toxicology, 1994; 86: 109-122.
85. 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.
86. Gibson, G., Orton, T., and Tamburini, P., Cytochrome P-450 induction by clofibrate, Biochem J., 1982; 203: 161-168.
87. Milton, M., Elcombe, C., and Gibson, G., On the mechanism of induction of microsomal cytochrome P450FVA1 and peroxisome proliferation in rat liver by clofibrate, Biochem. Pharmacol., 1990; 40: 2727-2732.
88. Orton, T. and Parker, G., The effect of hypolipidaemic 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.
89. 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 monolayers, Biochem. Pharmacol., 1990; 40: 2525-2534.
90. Sharma, R., Lake, B., and Gibson, G., Coinduction of microsomal cytochrome P-452 and the peroxisomal fatty acid β-oxidation pathway in the rat by clofibrate and di-(2-ethylhexyl)phthalate. Dose-response studies, Biochem. Pharmacol., 1988; 37: 1203-1206.
91. 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.
92. 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.
93. 450 gene family, J. Biol. Chem., 1987; 262: 801-810.
94. 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.
95. 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.
96. 450 that is not a lauric acid hydroxylase, Biochem. Pharmacol., 1991; 42: 2341-2349.
97. Hosokawa, M., Maki, T., and Satoh, T., Differences in the induction of carboxylesterase isozymes in rat liver microsomes by xenobiotics, Biochem. Pharmacol., 1988; 37: 2708-2711.
98. 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.
99. Hosokawa, M., Hirata, K., Nakata, F., Suga, T., and Satoh, T., Species differences in the induction of hepatic microsomal carboxylesterases caused by dietary exposure to di(2-ethylhexyl)phthalate, a peroxisome proliferator, Drug Metab. Dispos., 1994; 22: 889-894.
100. 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 β-oxidation by various hypolipidemic compounds, Biochem. Pharmacol., 1987; 36: 345-351.
101. 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 hydroxylation and phase II enzymes, Biochem. Pharmacol., 1989; 38: 1963-1969.
102. Visser, T., Kaptein, E., and Harpur, E., Differential expression and ciprofibrate induction of hepatic UDP-glucuronyltransferases for thyroxine and triiodothyronine in Fischer rats, Biochem. Pharmacol., 1991; 42: 444-446.
103. Barter, R. and Klaassen, C., Rat liver microsomal UDP-glucuronosyltransferase activity toward thyroxine: Characterization, induction and form specificity, Toxicol. Appl. Pharmacol., 1992; 115: 261-267.
104. 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-glutathione adducts, Toxicol. Appl. Pharmacol., 1996; 140: 30-38.
105. Furukawa, K., Numoto, S., Furuya, K., Furukawa, N., and Williams, G., Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital, Cancer Res., 1985; 54: 5011-5019.
106. Satoh, A., Ogata, K., Ogata, Y., and Kato, N., Decreased activity of xanthine oxidase in rat liver by feeding with di-(2-ethylhexyl) phthalate and clofibrate, Agric. Biol. Chem., 1990; 54: 2745-2746.
107. 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.
108. Foliot, A. and Beaune, P., Effects of microsomal enzyme inducers on glutathione-S-transferase isozymes in livers of rats and hamsters, Biochem. Pharmacol., 1994; 48: 293-300.
109. Moody, D., Loury, D., and Hammock, B., Epoxide metabolism in the liver of mice treated with clofibrate (ethyl-α-(p-chlorophenoxyisobutyrate), a peroxisome proliferator, Toxicol. Appl. Pharmacol., 1985; 78: 351-362.
110. 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. Biochem. Toxicol., 1995; 10: 87-94.
111. Conway, J., Tomaszewski, K., Olson, M., Cattley, R., Marsman, D., and Popp, J., Relationship of oxidative damage to the hepatocarcinogenecity of the peroxisome proliferators di(2-ethylhexyl)phthalate and WY14,643, Carcinogenesis, 1989; 10: 513-519.
112. Witzmann, F., Coughrie, M., Fultz, C., and Lipscomb, J., Effect of structurally diverse peroxisome proliferators on rat hepatic sulfotransferase, Chemico-Biological Interactions, 1996; 99: 73-84.
113. Kawai, Y., Takahashi, S., Satoh, A., and Kato, N., Decreased activity of xanthine dehydrogenase and serum uric acid in rats fed partially hydrogenated fish oil, Nutr. Res., 1993; 13: 1325-1330.
114. 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.
115. Lehotay, D., Gindler, J., and Paul, H., Effects of clofibrate on malic enzymes and phosphodiesterase activities, Horm. Metabol. Res., 1987; 19: 663-664.
116. Badr, M., Induction of peroxisomal enzyme activities by di-(2-ethylhexyl) phthalate in thyroidectomized rats with parathyroid replants, J. Pharmacol. Exp. Ther., 1992; 263: 1105-1110.
117. Hertz, R., Aurbach, R., Hashimoto, T., and Bar-Tana, J., Thyromimetic effect of peroxisomal proliferators in rat liver, Biochem. J., 1991; 274: 745-751.
118. 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.
119. 3 signaling pathways, Peroxisomes: Biology and Role in Toxicology and Disease, an International Symposium, Aspen, CO, 1995; 49.
120. Su, C. and Lardy, H., Induction of hepatic mitochondrial glycerophosphate dehydrogenase in rats by dehydroepiandrosterone, J. Biochem., 1991; 110: 207-213.
121. Song, M., Grieco, D., Rail, 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.
122. Zelewski, M. and Swierczynski, J., Clofibrate feeding increases cytoplasmic but not mitochondrial malic enzyme activity in rat kidney cortex, Cell Biochem. Function, 1989; 7: 97-103.
123. Olson, C. and Anderson, M., The acute toxicity of perfluorodecanoic acid in male rats and effects on tissue fatty acids, Toxicol. Appl. Pharmacol., 1983; 70: 362-372.
124. 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. Toxicol., 1990; 64: 26-30.
125. Zelewski, M. and Swierczynski, J., The effect of clofibrate feeding on the NADP-dehydrogenases activity in rat tissue, Biochim. Biophys. Acta, 1983; 758: 152-157.
126. 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.
127. 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.
128. Ochsner, M., Creba, J., Bentley, P., and Mukkassah-Kelly, S., Nafenopin, a hypolipidemic 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.
129. 2+ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome proliferator, Biochem. Pharmacol., 1992; 43: 595-605.
130. 2+-ATPase thiol integrity by ciprofibrate, a peroxisome proliferator, Biochem Pharmacol., 1993; 45: 2093-2098.
131. Vac, N., Schoonjans, K., Kosykh, V., Dallongeville, J., Fruchart, J-C., Staels, B., and Auwerx, J., Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor, J. Clin. Invest., 1995; 96: 741-750.
132. Nicholls-Grzemski, F., Calder, I., and Priestly, B., Peroxisome proliferators protect against paracetamol hepatotoxicity in mice, Biochem. Pharmacol., 1992; 43: 1395-1396.
133. Manautou, J., Hoivik, D., Tveit, A., Hart, S., Khairallah, E., and Cohen, S., Clofibrate pretreatment diminishes acetaminophen's selective covalent binding and hepatotoxicity, Toxicol. Appl. Pharmacol., 1994; 129: 252-263.
134. Sohlenius, A., Eriksson, A., Kimland, M., and DePierre, J., Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid β-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver, Pharmacol. Toxicol., 1993; 72: 90-93.
135. Motojima, K., Ohmori, A., Takino, Y., and Goto, S., Increase in the amount of elongation factor 2 in rat liver by peroxisome proliferators, J. Biochem., 1993; 114: 779-785.
136. 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; peroxisomal proliferation, mitochondrial dysfunctions and apoplexy, J. Nutr. Biochem., 1996; 7: 542-548.
137. Ishii, H., Horie, S., and Suga, T., Physiological role of peroxisomal β-oxidation in liver of fasted rats, J. Biochem., 1980; 87: 1855-1858.
138. Irizar, A. and Ioannides, C., Extrahepatic expression of P450 proteins in insulin-dependent diabetes mellitus, Xenobiotica, 1995; 25: 941-949.
139. 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.
140. Barnett, C., Gibson, G., Wolf, C., Flatt, P., and Ioannides, C., Induction of cytochrome P450 III and P450 IV family proteins in streptozotocin-induced diabetes, Biochem. J., 1990; 268: 765-769.
141. 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.
142. Okorodudu, A., Adegboyega, P., and Scholz, C., Intracellular calcium and hydrogen ions in diabetes mellitus, Ann. Clin. Lab. Sci., 1995; 25: 394-401.
143. Hummerich, H. and Soboll, S., Rapid stimulation of calcium uptake into rat liver by L-triiodothyronine, Biochem. J., 1989; 258: 363-367.
144. Pollera, M., Locci-Cubeddu, T., and Bergamini, E., Effect of cold adaptation on liver peroxisomes and peroxisomal oxidative activities of rat: a morphometric/stereologic and biochemical study, Intern. Physiol. Biochim., 1983; 91: 35-42.
145. 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.
146. Shmerling, M. and Filiushina, E., The ultrastructural of hepatocytes during the adaptation of rats to cold, Morphologiia, 1993; 105: 90-97.
147. 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.
148. Stott, W., Chemically induced proliferation of peroxisome: implications for risk assessment, Regulatory Toxicol. Pharmacol., 1988; 8: 125-159.
149. 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 Toxicol., 1996; 26: 365-481.
150. Reddy, J., Azarnoff, D., and Hignite, C., Hypolipidemic hepatic peroxisome proliferators form a novel class of chemical carcinogens, Nature, 1980; 283: 397-398.
151. 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.
152. Soliman, M., Cunningham, M., Morrow, J., Roberts, L. J., II, and Badr, M., Evidence against peroxisome proliferation-induced hepatic oxidative 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.
153. Conway, J. and Popp, J., Effect of the hepatocarcinogenic peroxisome proliferator WY-14,643 in vivo: no increase in ethane exhalation or hepatic cojugated dienes, Toxicol. Appl. Pharmacol., 1995; 135: 229-236.
154. Pineau, T., Hudgins, W. R., Liu, L., Chen, L., Sher, T., Gonzalez, F., and Samid, D. Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs, Biochem. Pharmacol., 1996; 52: 659-667.
155. 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.
156. IARC monographs on the evaluation of carcinogenic risks to humans, some pharmaceutical drugs, 1996; 66: 391-444.
157. 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.
158. Newman, T. and Hulley, S., Carcinogenicity of lipid-lowering drugs, J. Am. Med. Assoc., 1996; 275: 55-60.
159. Levy, G., Clinical pharmacokinetics of aspirin, Pediatrics, 1978; 62(Suppl): 867-872.
160. Wientjes, M. G. and Levy, G., Nonlinear pharmacokinetics of aspirin in rats, J. Pharmacol. Exp. Ther., 1988; 245: 809-815.
161. Nelson, E., Hanano, M., and Levy, G., Comparative pharmacokinetics of salicylate elimination in man and rats, J. Pharmacol. Exp. Ther., 1966; 153: 159-166.
162. Morris, M., Pharmacokinetics and protein binding of salicylate metabolites in rats, Drug Metab. Dispos., 1990; 18: 809-811.
163. Owen, M. and Halestrap, A., The mechanism by which mild respiratory chain inhibitors inhibit hepatic gluconeogenesis, Biochem. Biophys. Acta, 1993; 1142: 11-22.
164. Bojes, H., Sausen, P., Cattley, R., Keller, B., and Thurman, R.,
165. Mousseau, D. and Butterworth, R., Current theories on the pathogenesis of hepatic encephalopathy, Proc. Soc. Exp. Biol. Med., 1994; 206: 329-344.
166. Glick, B. and Rothman, J., Possible role for fatty acyl-coenzyme A in intracellular protein transport, Nature, 1987; 326: 309-312.
167. King, M., Pugazhenthi, S., Khandelwal, R., and Sharma, R., Elevated N-myristoyl transferase activity is reversed by sodium orthovanadate in streptozotocin-induced diabetic rat, Bichem. Biophys. Acta, 1993; 1165: 259-262.
168. 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.
169. Pounds. J., The role of cell calcium in current approaches to toxicology, Environ. Health Perspect., 1990; 84: 7-15.
170. Cheung, J., Bonaventure, J., Malis, C., and Leaf, A., Calcium and ischemic injury, N. Engl. J. Med., 1986; 314: 1670-1676.
171. 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.
172. Farber, J., The role of calcium ions in toxic cell injury, Environ. Health Perspect., 1990; 84: 107-111.
173. 2+, J. Biol. Chem., 1984; 259: 6612-6615.
174. Nishizuki, Y., Intracellular signaling by hydrolysis of phospholipids and protein kinase C, Science, 1992; 258: 607-614.
175. 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.
176. Bojes, H. and Thurman, R., Peroxisome proliferators inhibit acyl-CoA synthetase and stimulate protein kinase C in vivo, Toxicol. Appl. Pharmacol., 1994; 126: 233-239.
177. 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.
178. Rokos, C. and Ledwith, B., Peroxisome proliferators activate extracellular signal-regulated kinases in immortalized mouse liver cells, J. Biol. Chem., 1997; 272: 13452-13457.
179. Bond, J. and Butler, P. E., Intracellular proteases, Annu. Rev. Biochem., 1987; 56: 333-364.
180. Goldstein, D., Feistner, G., Faull, K., and Tower, K., Plasticizers as contaminants in commercial ethanol, Alcoholism: Clin. Exp. Res., 1987; 11: 521-524.
181. Kaptein, E., Thyroid hormone metabolism and thyroid diseases in chronic renal failure, Endocrine Rev., 1996; 17:45-63.
182. Cohn, J., Ingbar, S., and Braverman, L., Thyrotoxicosis due to ingestion of excess thyroid hormone, Endocrine Rev., 1989; 10: 113-124.
183. Cayen, M., Disposition, metabolism and pharmacokinetics of antihyperlipidemic agents in laboratory animals and man, Pharmacol. Ther., 1985; 29: 157-204.
184. 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.
185. Agarwal, D., Eustis, S., Lamb, C., and Kluwe, W., Influence of dietary zinc on di(2-ethylhexyl) phthalate-induced testicular atrophy and zinc depletion in adult rats, Toxicol. Appl. Pharmacol., 1986; 84: 12-24.
186. 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.
187. s) on rat Leydig cell function in vitro, Toxicologist, 1995; 15: 1291.
188. Eagon, P., Chander, N., Epley, M., Elm, M., Brady, E., and Rao, K., Di(2-ethylhexyl)phthalate-induced changes in liver estrogen metabolism and hyperplasia. Int. J. Cancer, 1994; 58: 736-743.
189. Eagon, P., M., Elm, Epley, M., Schinozuka, H., and Rao, K., Peroxisome proliferators: sex steroid receptors and metabolism in hepatic hyperplasia and neoplasia, Toxicologist, 1996; 15: 1057.
190. Corton, J. C., Bocos, C., Moreno, E. S., Merritt, A., Marsman, D., Sausen, P., Cattley, R. and Gustafsson, J-A., Rat 17 β-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene, Mol. Pharmacol., 1996; 50: 1157-1166.
191. Corton, J. C., Bocos, C., Moreno, E. S., Merritt, A., Cattley, R. C., and Gustafsson, J-A., Peroxisome proliferators alter the expression of estrogen metabolizing enzymes, Biochimie, 1997; 79: 151-162.
192. 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.
193. Lamb, E. and Bennett, S., Epidemiological studies of male factors in infertility, Ann. N. Y. Acad. Sci., 1994; 709: 165-178.
194. 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.
195. 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.
196. 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.
197. Nathan, L. and Chaudhuri, G., Estrogens and atherosclerosis, Annu. Rev. Pharmacol. Toxicol., 1997; 37: 477-515.
198. Riggs, L. and Melton, L. J., The prevention and treatment of osteoporosis, N. Engl. J. Med., 1992; 327: 620-627.
199. Mochizuki, Y., Furukaea, K., and Sawada, N., Effects of various concentrations of ethyl-α-p-chlorophenoxyisobutyrate (clofibrate) on diethylnitrosoamine-induced hepatic tumorigenesis in the rat, Carcinogenesis, 1982; 3: 1027-1029.
200. Voskoboinik, I., Drew, R. and Ahokas, J. T., Peroxisome proliferator nafinopin potentiated cytotoxicity and genotoxicity of cyclophosphamide in the liver and bone marrow cells, Chemico. Biol. Inter., 1997; 105: 81-97.
201. Patrono, C., Aspirin as an antiplatelet drug, N. Engl. J. Med., 1994; 330: 1287-1294.
202. 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.
203. Youssef, J. and Badr, M., Activated Kupffer cells attenuate the liver response to the peroxisome proliferator perfluorooctanoic acid, Mol. Cell. Biochem., 1997; 169: 143-147.
204. Bojes, H. and Thurman, R., Peroxisome proliferators activate Kupffer cells in vivo, Cancer Res., 1996; 56: 1-4.
205. Smith, A., Francis, J., Walters, D., and Lake, B., Protection against iron-induced uroporphyria in C57BL/10ScSn mice by the peroxisome proliferator nafenopin, Biochem. Pharmacol., 1990; 40: 2564-2568.
206. 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.
207. 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.
208. Yamada, J., Sakuma, M., Ikeda, T., Fukuda, K., and Suga, T., Characteristics of dehydroepiandrosterone as a peroxisome proliferator, Biochem. Biophys. Acta, 1991; 1092: 233-243.
209. Becker, C. and Harris, R., Influence of valproic acid on hepatic carbohydrate and lipid metabolism, Arch. Biochem. Biophys., 1983; 223: 381-392.