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2000 | 47 | 4 | 1129-1136
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Influence of acetaminophen and trichloroethylene on liver cytochrome P450-dependent monooxygenase system.

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The aim of the study was to evaluate the effect of acetaminophen (APAP) and/or trichloroethylene (TRI) on the liver cytochrome P450-dependent monooxygenase system, CYP2E1 and CYP1A2 (two important P450 isoforms), and liver glutathione (GSH) content in rats. Rats were given three different doses of APAP (250, 500 and 1000 mg/kg b...) and then the above-mentioned parameters were measured for 48 h. The lowest APAP dose produced small changes in the cytochrome P450 content of liver. At 500 mg/kg APAP increased the cytochrome P450 content to 230% of the control. The inductive effect was seen at 1000 mg/kg dose but at 24 h and later. NADPH-cytochrome P450 reductase activity was the highest after the lowest dose of APAP, while after the highest dose it was equal to the control value. TRI increased both the cytochrome P450 content and the NADPH-cytochrome P450 reductase activity. When TRI was combined with APAP, both these parameters increased in the first hours of observation, but they returned to the control values at 24 h. When APAP was given at 250 mg/kg, GSH levels decreased to 55% of the control at 8 h and returned to the control values at 24 h. The higher doses of APAP decreased GSH levels more than the lowest dose, but after 24 h GSH levels did not differ from those of the control. When TRI was given at 250 mg/kg, the GSH levels decreased to 68% of the control at 2 h and then they increased gradually and tended to exceed the control values at 48 h. The effect of TRI combined with APAP on the level of GSH was virtually the same as that of APAP alone given at 500 mg/kg.

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  • Department of Histology and Embryology, Silesian School of Medicine-Ligota, Katowice, Poland
  • Department of Toxicology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
  • Department of Toxicology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
  • Department of Histology and Embryology, Silesian School of Medicine-Ligota, Katowice, Poland
  • Department of Histology and Embryology, Silesian School of Medicine-Ligota, Katowice, Poland
  • Department of Histology and Embryology, Silesian School of Medicine-Ligota, Katowice, Poland
  • Department of Histology and Embryology, Silesian School of Medicine-Ligota, Katowice, Poland
  • Department of Toxicology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
  • Adams, J.D., Lauterburg, B.H. & Mitchell, J.R. (1983) Plasma glutathione and glutathione disulfide in the rat: Regulation and response to oxidative stress. J. Pharmacol. Exp. Ther. 227, 749-754.
  • Amimoto, T., Matsura, T., Koyama, S.-Y., Nakanishi, T., Yamada, K. & Kaiyama, G. (1995) Acetaminophen-induced hepatic injury in mice: The role of lipid peroxidation and effects of pretreatment with coenzyme Q10 and α-tocopherol. Free Radic. Biol. Med. 19, 169-176.
  • Bruckner, J.V., Davis, B.D. & Blancato, J.N. (1989) Metabolism, toxicity, and carcinogenicity of trichloroethylene. Crit. Rev. Toxicol. 20, 31-50.
  • Comporti, M., Maellaro, E., Del Bello, B. & Casini, A.F. (1991) Glutathione depletion: Its effects on other antioxidant systems and hepatocellular damage. Xenobiotica 21, 1067-1076.
  • Corcoran, G.B. & Wong, B.K. (1986) Role of glutathione in prevention of acetaminophen-induced hepatotoxicity by N-acetyl-L-cysteine in vivo: Studies with N-acetyl-D-cysteine in mice. J. Pharmacol. Exp. Ther. 238, 54-61.
  • Dahlin, D.C., Miwa, G.T., Lu, A.Y. & Nelson, E.C. (1984) N-acetyl-p-benzoquinone imine: A cytochrome P450-mediated oxidation product of acetaminophen. Proc. Natl. Acad. Sci. U.S.A. 81, 1327-1331.
  • Dallner, G. (1974) Isolation of rough and smooth microsomes general. Methods Enzymol. 31, 191-215.
  • Dekant, W., Schulz, A., Metzeler, M. & Henschler, D. (1986) Absorption, elimination and metabolism of trichloroethylene: A quantitative comparison between rats and mice. Xenobiotica 16, 143-152.
  • Elcombe, C.R., Rose, M.S. & Pratt, I.S. (1985) Biochemical, histological, and ultrastructural changes in rat and mouse liver following the administration of trichloroethylene: Possible relevance to species differences in hepatocarcinogenicity. Toxicol. Appl. Pharmacol. 79, 365-376.
  • Estabrook, R.W. & Werringloer, J. (1978) The measurement of difference spectra: Application to the cytochromes of microsomes. Methods Enzymol. 52, 212-220.
  • Geoptar, A.R., Scheerens, H. & Vermeulen, N.P.E. (1995) Oxygen and xenobiotics reductase activities of cytochrome P-450. Crit. Rev. Toxicol. 25, 25-65.
  • Guengerich, F.P. (1995) Influence of nutrients and other dietary materials on cytochrome P-450 enzymes. Am. J. Clin. Nutr. 61 (Suppl.), 651S-658S.
  • Guengerich, F.P., Kim, D.H. & Iwasaki, M. (1991) Role of human cytochrome P-450IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol. 4, 168-179.
  • Halliwell, B.& Gutteridge, J.M.C. (1989) Protection against oxidants in biological systems: The superoxide theory of oxygen toxicity; in Free Radicals in Biology and Medicine (Halliwell, B., Gutteridge, J.M.C., eds.) pp. 86-187, Oxford University Press, New York.
  • Hanioka, N., Omae, E., Yoda, R., Jinno, H., Nishimura, T. & Ando, M. (1997) Effect of trichloroethylene on cytochrome P450 enzymes in the rat liver. Bull. Environ. Contam. Toxicol. 58, 628-635.
  • Hodges, T.K. & Leonard, R.T. (1974) Purification of a plasma membrane-bound adenosine triphosphatase from plant roots. Methods Enzymol., 32, 392-406.
  • Koop, D.R., Crump, B.L., Nordblom, G.D. & Coon, M. (1985) Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: Ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazyd. Proc. Natl. Acad. Sci. U.S.A. 82, 4065-4069.
  • Kuralay, F., Akarca, U.S., Ozutemitz, O., Kutay, F. & Batur, Y. (1998) Possible role of glutathione in prevention of acetaminophen-induced hepatotoxicity enhanced by fish oil in male Wistar rats. J. Toxicol. Environm. Health Part A 53, 223-229.
  • Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.
  • Lowry, O.H., Rosebrough, N.J., Farr, A.L. & Randal, R.J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275.
  • Miller, R.E. & Guengerich, F.P. (1983) Metabolism of trichloroethylene in isolated hepatocytes, microsomes, and reconstituted enzyme systems containing cytochrome P-450. Cancer Res. 43, 1145-1152.
  • Moore, M., Thor, H., Moore, G., Nelson, S., Moldeus, P. & Orrenius, S. (1985) The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+. J. Biol. Chem. 260, 13035-13040.
  • Nakajima, T., Wang, R.-S., Elovaara, E., Park, S.S., Gelboin, H.V. & Vainio, H. (1992) A comparative study on the contribution of cytochrome P450 isozymes to metabolism of benzene, toluene and trichloroethylene in rat liver. Biochem. Pharmacol. 43, 251-257.
  • Nelson, E.B., Montes, M. & Goldstein, M. (1990) Effectiveness of metyrapone in the treatment of acetaminophen toxicity in mice. Toxicology, 17, 73-81.
  • Ogino, K., Hobara, T., Kobayashi, H., Ishiyama, H., Gotoh, M., Imamura, A. & Egami, N. (1991) Lipid peroxidation induced by trichloroethylene in rat liver. Bull. Environ. Contam. Toxicol. 46, 417-421.
  • Okino, T., Nakajima, T. & Nakano, M. (1991) Morphological and biochemical analyses of trichloroethylene hepatotoxicity: Differences in ethanol- and phenobarbital-pretreated rats. Toxicol. Appl. Pharmacol. 108, 379-389.
  • Plewka, A. & Kamiński;, M. (1996) Influence of cholesterol and protein diet on liver cytochrome P-450-dependent monooxygenase system in rats. Exp. Toxicol Pathol. 48, 249-253.
  • Plewka, A., Kamiński;, M. & Plewka, D. (1998) Ontogenesis of hepatocyte respiration processes in relation to metabolism of xenobiotics. Mech. Ageing Dev. 105, 197-207.
  • Plewka, A., Bienioszek, M. & Plewka, D. (1994) Changes in the male rat hepatic cytochrome P-450 level, heme oxygenase and δ-aminolevulinic acid synthase activities at various stages of life. Mech. Ageing Dev. 74, 79-88.
  • Plewka, A. & Bienioszek, M. (1994) Effects of age, phenobarbital, β-naphthoflavone and dexamethasone on rat hepatic heme oxygenase. Arch. Toxicol. 68, 32-36.
  • Rikans, L.E. & Kasanka, S.G. (1984) Effect of aging on liver glutathione levels and hepatocellular injury from carbon tetrachloride, allyl alcohol or galactosamine. Drug Chem. Toxicol. 7, 595-604.
  • Rouisse, L. & Chakrabarti, S.K. (1986) Dose-dependent metabolism of trichloroethylene and its relevance to hepatotoxicity in rats. Environ. Res. 40, 450-458.
  • Ryu, B.K., Ahn, B.O., Oh, T.Y., Kim, S.H., Kim, W.B. & Lee, E.B. (1998) Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats. Arch. Pharm. Res. 21, 508-513.
  • Tamburini, P.P. & Schenkman, J.B. (1986) Difference in the mechanism of functional interaction betwen NADPH-cytochrome P-450 reductase an its redox partners. Mol. Pharmacol. 30, 178-185.
  • Wang, R.-S., Nakajima, T., Tsuruta, H. & Honma, T. (1996) Effect of exposure to four organic solvents on hepatic cytochrome P-450 isozymes in rat. Chem.-Biol. Interact. 99, 239-252.
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