1 Treatment of rats with hypolipidaemic drugs or with the plasticizer di-2-ethyl hexyl phthalate caused significant alterations in the concentration of certain plasma proteins.
2 Certain proteins showed dose-dependent increases, in other cases the plasma concentrations fell in treated animals.
3 The changes were quite distinct from the changes in plasma proteins which occur during the acute-phase response to inflammatory agents.
4 Some changes appeared specific to agents which produce peroxisome proliferation in liver, other alterations appeared associated with mild, but sustained, liver injury.
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References
1.
Axelsen, N.H., Kroll, J. & Weeke, B. (1973). A manual of quantitative immunoelectrophoresis , Universitetsforlaget, Oslo.
2.
Barnard, S.D., Molello, J.A., Caldwell, W.J. & Le Beau, J.E. (1980). Comparative ultrastructural study of rat hepatocytes after treatment with the hypolipidaemic agents, probucol, clofibrate and fenofibrate . J. Toxicol. Environ. Health, 6, 547-557.
3.
Baumann, H., Firestone, G.L., Burgess, T.L., Gross, K.W., Yamamoto, K.R. & Held, W.A. (1983). Dexamethasone regulation ofaj-acid glycoprotein and other acute phase reactants in rat liver and hepatoma cells. J. Biol. Chem., 258, 563-570.
4.
Blane, G.F. & Pinaroli, F. (1980). Fenofibrate, etudes de toxicologie animale en rapport avec les effets secondaires chez les malades. Nouv. Presse Med., 9, 3737-3746.
5.
Blumcke, S., Schwartzkopff, W., Lobeck, H., Edmondson, W.A., Prentice, D.E. & Blane, G.F. (1983). Influence of fenofibrate on cellular and subcellular liver structure in hyperlipidaemic patients. Atherosclerosis , 46, 105-116.
6.
Cohen, A.J. & Grasso, P. (1981). Review of the hepatic response to hypolipidaemic drugs in rodents and assessment of its toxicological significance to man. Food Cosmet. Toxicol., 19, 585-605.
7.
Grasso, P. & Gray, T.J.B. (1977). Long term studies on chemically induced liver enlargement in the rat. III, Structure and behavior of the hepatic nodular lesions induced by Ponceau MX. Toxicology, 7, 327-347.
8.
Gray, T.J.B., Beamand, J.A., Lake, B.G., Foster, J.R. & Gangolli, S.D. (1982). Peroxisome proliferation in cultured rat hepatocytes produced by clofibrate and phthalate ester metabolites . Toxicol. Lett.10, 273-279.
9.
Hanefeld, M., Kemmer, Ch., Leonhardt, W., Kunze, K.D., Jaross, W. & Haller, H. (1980). Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. Atherosclerosis, 36, 159-172.
10.
Hinton, R.H., Dobrota, M. & Mullock, B.M. (1980). Haptoglobin mediated transport of haemoglobin from serum into bile. FEBS Lett., 112, 247-250.
11.
Iarc (1979). Monograph on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, vol. 20, Some Halogenated Hydrocarbons. Lyon: IARC.
12.
Kawai, T. (1973). Clinical aspects of the plasma proteins. Chapter 21. Plasma protein changes in acute phase responses. In The Practice of Clinical Immunology, 2nd edn, ed. R.A. Thompson.London: E. Arnold.
13.
Koj, A. ( 1974). Acute phase reactants. In Structure and Function of Plasma Proteins vol. 1., ed. A. C. Allison, pp. 73-125. New York: Plenum Press.
14.
Kushner, I. (1982). The phenomenon of the acute phase response. Ann. N. Y. Acad. Sci., 389, 39-48.
15.
Mann, A.H. (1981). Liver toxicity of dialkyl phthalate plasticizers. MSc dissertation, University of Surrey, Guildford.
16.
Miller, L.L. & John, D.W. (1980). In Plasma Protein Metabolism, eds M. A. Rothschild & T. Waldmann, pp. 207-222.New York: Academic Press.
17.
Miller, E.C. & Miller, J.A. (1981). Mechanism of chemical carcinogenesis. Cancer, 47, 1055-1064.
18.
Price, S.C., Hinton, R.H., Hall, D.E., Grasso, P. & Bridges, J.W. (1982). Accumulation of lipid-rich lysosomes in the livers and kidneys of animals treated with hypolipidaemic agents. Biochem. Soc. Trans., 10, 244.
19.
Reddy, J.K. & Lalwani, N.D. (1984). Carcinogenesis by hepatic peroxisome proliferators. Evaluation of the risk of hypolipidaemic drugs and industrial plasticisers to humans. CRC Crit. Rev. Toxicol.12, 1-58.
20.
Reddy, J.H., Lalwani, N.D., Qureshi, S.A., Reddy, M.K. & Moehle, C.M. (1984). Induction of hepatic peroxisome proliferation in non-rodent species including primates. Pathology, 114, 171-183.
21.
Rinkins, S.J. & Legator, M.S. (1979). Chemical characterisation of 465 known or suspect carcinogens and their correlation with mutagenic activity in the Salmonella typhimurium system. Cancer Res., 39, 3289-3318.
22.
Williams, C.A. & Wemyss, C.T. (1961). Changes produced in mouse plasma proteins by acute bacterial infections. J. Exp. Med., 114, 311-325.
