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The Pharmaceutical Society of Korea (대한약학회)
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Pretreatment with 1,8-Cineole Potentiates Thioacetamide-Induced Hepatotoxicity and Immunosuppression

  • Published : 2004.07.01
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Abstract

The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzy-loxyresorufin- and pentoxyresorufin-D-dealkylases and erythromycin N-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioace-tamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepato-toxicity and immunotoxicity.

Keywords

References

  1. Blank, J. A., Sweatlock, J., Gasiewicz, T. A., and Luster, M. I., $\alpha$-Naphthoflavone antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin nduced murine ethoxyresorufin O-deethylase activity nd immunosuppression. Mol. Pharmacol., 32, 168-172 (1987)
  2. Bresnick, E., Induction of cytochrome P450 1 and P450 2 byxenobiotics. ln: Schenkman, J. B., Greim,H. (Eds.), Handbook of Experimental Pharmacology, Vol. 105, Springer-Verlag, Berlin, pp. 503-524 (1993)
  3. Guengerich, F. P. and Shimada, T., Oxidation of toxic and carcinogenic chemicals by human cytochrome P450 enzymes. Chem. Res. Toxicol., 4, 391-407 (1991) https://doi.org/10.1021/tx00022a001
  4. Holsapple, M. P., Eads, M., Stevens, W. D., Wood, S. C., Kaminski, N. E, Morris, D. L., Poklis, A., Kaminski, E. J., and Jordan, S. D., Immunosuppression in adult B6C3F1 mice by chronic exposure to ethanol in a liquid diet. Immunophar-macology. 26, 31-51 (1993) https://doi.org/10.1016/0162-3109(93)90064-W
  5. Huang, Y. B., Fang, J. Y., Hung, C. H., Wu, P. C., and Tsai, Y. H., Cyclic monoterpene extract from cardamom oil as a skin permeation enhancer for indomethacin: in vitro and in vivo studies. Biol. Pharm. Bull., 22, 642-646 (1999) https://doi.org/10.1248/bpb.22.642
  6. Hunter, A. L., Holscher, M. A., and Neal, R. A., Thioacetamide- induced hepatic necrosis. I. Involvement of the mixedfunction oxidase enzyme system. J. Pharmacol. Exp. Ther., 200,439-448 (1977)
  7. Jeong, T. C., Gu, H. K., Park, J. I., Yun, H. I., Kim, H. C., Ha, C. S., and Roh, J. K., Pretreatmentof male BALB/c mice with $\beta$-ionone potentiates thioacetamide-induced hepatotoxicity. Toxicol. Lett., 105, 39-46 (1999) https://doi.org/10.1016/S0378-4274(98)00386-5
  8. Jeong, H. G. and Yun, C. H., Induction of rat hepatic cytochrome P450 enzymes by myristicin. Biochem. Biophys. Res. Commun., 217, 966-971 (1995) https://doi.org/10.1006/bbrc.1995.2864
  9. Jeong, H. G., Yun, C. H., Jeon, Y. J., Lee, S. S., and Yang, K. H., Suppression of cytochrome P450 (Cyp 1a-1) induction in mouse hepatoma Hepa-1c1c7 cells by methoxsalen. Biochem. Biophys. Res. Commun., 208, 1124-1130 (1995a) https://doi.org/10.1006/bbrc.1995.1450
  10. Jeong, T. C., Kim, H. J., Yun, C. H., Lee, S. S., Yang, K. H., Han, S. S., and Roh, J. K., Induction of liver cytochrome P4502B1 by $\beta$-ionone in Sprague Dawley rats. Biochem. Biophys. Res. Commun., 216, 198-202 (1995b) https://doi.org/10.1006/bbrc.1995.2610
  11. Juergens, U. R., Dethlefsen, U., Steinkamp, G., Gillissen, A, Repges, R., and Vetter, H., Anti-inflammatory activity of 1,8-cineole (eucalyptol) in bronchial asthma: a double-blind placebo-eontrolled trial. Respir. Med., 97, 250-256 (2003) https://doi.org/10.1053/rmed.2003.1432
  12. Juergens, U. R., Stober, M., and Vetter, H., Inhibitionof cytokine production and arachidonic acid metabolism by eucalyptol (1,8-cineole) in human blood monocytes in vitro. Eur. J. Med. Res., 3, 508-510 (1998)
  13. Kaminski, N. E., Barnes, D. W., Jordan, S. D., and Holsapple, M. P., The role of metabolism in carbon tetrachloride-mediated immunosuppression: In vivo studies. Toxicol. Appl. Pharmacol., 102, 9-20 (1990) https://doi.org/10.1016/0041-008X(90)90079-A
  14. Kim, K. H., Bae, J. H., Cha, S. W., Han, S. S., Park, K. H., and Jeong, T. C., Role of metabolic activation by cytochrome P450 in thioacetamide-induced suppression of antibody response in male BALB/c mice. Toxicol. Lett., 114, 225-235 (2000) https://doi.org/10.1016/S0378-4274(00)00168-5
  15. Koop, D. R., Hydroxylation or p-nitrophenol by rabbit ethanolinducible cytochrome P-450 isozyme 3a. Mol. Pharmacol., 29, 399-404 (1986)
  16. Laemmli, U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685 (1970) https://doi.org/10.1038/227680a0
  17. Lee, J. W., Shin, K. D., Lee, M., Kim, E. J., Han, S. S., Han, M. Y., Ha, H., Jeong, T. C., and Koh, W. S., Role of metabolism by flavin-eontaining monooxygenase in thioacetarnideinduced immunosuppression. Toxicol. Lett., 136, 163-172 (2003) https://doi.org/10.1016/S0378-4274(02)00333-8
  18. Liu, J., Liu, Y., BUllock, P., and Klaassen, C. D., Suppression of liver cytochrome P450 by a-hederin: relevance to hepatoprotection. Toxieol. Appl. Pharmacol., 134, 124-131 (1995) https://doi.org/10.1006/taap.1995.1175
  19. Lubet, R. A., Meyer, R. T., Cameron, R. W., Nims, R. W., Burke, M. D., Wolff, J., and Guengerich, F. P., Dealkylation of pentoxyresorufin: rapid and sensitive assay for measuring inductionof cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat. Arch. Biochem. Biophys., 238, 43-48 (1985) https://doi.org/10.1016/0003-9861(85)90138-9
  20. Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. J., Protein measurement with the folin phenol reagent. J. Biol. Chem., 193, 265-275 (1951)
  21. Mangipudy, R. S., Chanda, S., and Mehendale, H. M., Tissue repair response as a function of dose in thioacetamide hepatotoxicity. Environ. Health Perspect., 103, 260-267 (1995) https://doi.org/10.2307/3432546
  22. M,itsuo, M., Masaki, S., and Tsutimu, S., Oxidation of 1,8-cineole, the monoteroene cyclicether originated from Eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab. Dispos., 29, 200-205 (2000)
  23. Nash, T., The colorimetrical estimation of formaldehyde by means of the Hanttsch reaction. Biochem. J., 55, 416-421 (1953)
  24. Nebbia, C., Biotransformation enzymes as determinants of xenobiotic toxicity in domestic animals. Veterinary J., 161, 238-252 (2001) https://doi.org/10.1053/tvjl.2000.0561
  25. de Oliveira, A. C. A. X., Fidalgo-Neto, A. A., and Paumgartten, E J. R., In vitro inhibition of liver monooxygenases by $\beta$-ionone, 1,8-cineole, (-)-menthol and terpineol. Toxicology, 135, 33-41 (1999) https://doi.org/10.1016/S0300-483X(99)00043-8
  26. de Oliveira, A. C. A. X., Ribeiro-Pinto, L. E., and Paumgartten, E. J. R., In vitro inhibition of CYP2B1 monooxyganases by $\beta$-myrcene and other monoterpenoid compounds. Toxicology, 92, 39-46 (1997a) https://doi.org/10.1016/0300-483X(94)90166-X
  27. de Oliveira, A. C. A X., Ribeiro-Pinto, L. E, Otto, S. S., Gonvalves, A, and Paumgartten, E. J. R., Induction of liver monooxygenases by $\beta$-myrcene. Toxicology, 124, 135-140 (1997b) https://doi.org/10.1016/S0300-483X(97)00144-3
  28. Sabbele, N. R., van Oudenaren, A., Hooijkaas, H., and Benner, R., The effect of corticosteroids upon murine B cells in vivo and in vitro as determined in the LPS-eulture system. J. Immunol., 62, 285-290 (1987)
  29. Surh, Y. J., Lee, K. K, Park, S. T., Mayne, A., Liem, J., and Miller, A., Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis or tumorigenesis by vinyl carbamate and N-nitrosodimethylamine. Carcinogenesis 16, 2467-2471 (1995) https://doi.org/10.1093/carcin/16.10.2467
  30. Wang, T., Apte, U., and Mehendale, H. M., Cytochrome P4502E1 induction increases thioacetamide liver injury in diet-restricted rats. Drug Metab. Dispos., 29, 1088-1095 (2001)
  31. Wang, T., Shankar, K., Ronis, M. J., and Mehendale, H. M., Potentiation of thioacetamide liver injury in diabetic rats is due to induced CYP2E1. J. Pharmacol. Exp. Ther., 294, 473-479 (2000)
  32. White, K. L., Jr., Lysy, H. H., and Holsapple, M. P., Immunosuppression by polycyclic aromatic hydrocarbons: a structureactivity relationship in B6C3F1 and DBA/2 mice. Immuno-pharmacology, 9, 155-164 (1985) https://doi.org/10.1016/0162-3109(85)90011-6