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Archives of Pharmacal Research

, Volume 27, Issue 7, pp 781–789 | Cite as

Pretreatment with 1,8-cineole potentiates thioacetamide-lnduced hepatotoxicity and immunosuppression

  • Nam Hee Kim
  • Sun Hee Hyun
  • Chun Hua Jin
  • Sang Kyu Lee
  • Dong Wook Lee
  • Tae Won Jeon
  • Jae Sung Lee
  • Young Jin Chun
  • Eung Seok Lee
  • Tae Cheon Jeong
Research Articles Articles

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-O-dealkylases and erythromycinN-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 thioacetamide, 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 hepatotoxicity and immunotoxicity.

Key words

Cytochrome P450 1,8-Cineole Metabolic activation Thioacetamide Hepatotoxicity Immunotoxicity 

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References

  1. Blank, J. A., Sweatlock, J., Gasiewicz, T. A., and Luster, M.I., α- Naphthoflavone antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced murine ethoxyresorufinO-deethylase activity and immunosuppression.Mol. Pharmacol., 32, 168–172 (1987).Google Scholar
  2. Bresnick, E., Induction of cytochrome P450 1 and P450 2 by xenobiotics. In: Schenkman, J. B., Greim, H. (Eds.), Handbook of Experimental Pharmacology, Vol. 105, Springer-Verlag, Berlin, pp. 503–524 (1993).Google Scholar
  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).PubMedCrossRefGoogle Scholar
  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.Immunopharmacology. 26, 31–51 (1993).PubMedCrossRefGoogle Scholar
  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 andin vivo studies.Biol. Pharm. Bull., 22, 642–646 (1999).PubMedGoogle Scholar
  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).PubMedGoogle Scholar
  7. Jeong, T. C., Gu, H. K., Park, J. I., Yun, H. I., Kim, H. C., Ha, C. S., and Roh, J. K., Pretreatment of male BALB/c mice with β-ionone potentiates thioacetamide-induced hepatotoxicity.Toxicol. Lett., 105, 39–46 (1999).PubMedCrossRefGoogle Scholar
  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).PubMedCrossRefGoogle Scholar
  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).CrossRefGoogle Scholar
  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 P450 2B1 by p-ionone in Sprague Dawley rats.Biochem. Biophys. Res. Commun., 216, 198–202 (1995b).CrossRefGoogle Scholar
  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-controlled trial.Respir. Med., 97, 250–256 (2003).PubMedCrossRefGoogle Scholar
  12. Juergens, U. R., Stober, M., and Vetter, H., Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1,8-cineole) in human blood monocytesin vitro.Eur. J. Med. Res., 3, 508–510 (1998).PubMedGoogle Scholar
  13. Kaminski, N. E., Barnes, D. W., Jordan, S. D., and Holsapple, M. P., The role of metabolism in carbon tetrachtoridemediated immunosuppression:In vivo studies.Toxicol. Appl. Pharmacol., 102, 9–20 (1990).PubMedCrossRefGoogle Scholar
  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).PubMedCrossRefGoogle Scholar
  15. Koop, D. R., Hydroxylation or p-nitrophenol by rabbit ethanolinducible cytochrome P-450 isozyme 3a.Mol. Pharmacol., 29, 399–404 (1986).PubMedGoogle Scholar
  16. Laemmli, U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680–685 (1970).PubMedCrossRefGoogle Scholar
  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-containing monooxygenase in thioacetamideinduced immunosuppression.Toxicol. Lett., 136, 163–172 (2003).PubMedCrossRefGoogle Scholar
  18. Liu, J., Liu, Y., Bullock, P., and Klaassen, C. D., Suppression of liver cytochrome P450 by α-hederin: relevance to hepatoprotection.Toxicol. Appl. Pharmacol., 134, 124–131 (1995).PubMedCrossRefGoogle Scholar
  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 induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat.Arch. Biochem. Biophys., 238, 43–48 (1985).PubMedCrossRefGoogle Scholar
  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).PubMedGoogle Scholar
  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).PubMedCrossRefGoogle Scholar
  22. Mitsuo, M., Masaki, S., and Tsutimu, S., Oxidation of 1,8-cineole, the monoteroene cyclic ether originated fromEucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes.Drug Metab. Dispos., 29, 200–205 (2000).Google Scholar
  23. Nash, T., The colorimetrical estimation of formaldehyde by means of the Hantzsch reaction.Biochem. J., 55, 416–421 (1953).PubMedGoogle Scholar
  24. Nebbia, C., Biotransformation enzymes as determinants of xenobiotic toxicity in domestic animals.Veterinary J., 161, 238–252 (2001).CrossRefGoogle Scholar
  25. de Oliveira, A. C. A. X., Fidalgo-Neto, A. A., and Paumgartten, F. J. R.,In vitro inhibition of liver monooxygenases by β-ionone, 1,8-cineole, (-)-menthol and terpineol.Toxicology, 135, 33–41 (1999).CrossRefGoogle Scholar
  26. de Oliveira, A. C. A. X., Ribeiro-Pinto, L. F., and Paumgartten, F. J. R.,In vitro inhibition of CYP2B1 monooxygenases by β-myrcene and other monoterpenoid compounds.Toxicology, 92, 39–46 (1997a).Google Scholar
  27. de Oliveira, A. C. A. X., Ribeiro-Pinto, L. F., Otto, S. S., Gonvalves, A., and Paumgartten, F. J. R., Induction of liver monooxygenases by β-myrcene.Toxicology, 124, 135–140 (1997b).CrossRefGoogle Scholar
  28. Sabbele, N. R., van Oudenaren, A., Hooijkaas, H., and Benner, R., The effect of corticosteroids upon murine B cellsin vivo andin vitro as determined in the LPS-culture system.J. Immunol., 62, 285–290 (1987).Google Scholar
  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 andN-nitrosodimethylamine.Carcinogenesis 16, 2467–2471 (1995).PubMedCrossRefGoogle Scholar
  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).Google Scholar
  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).PubMedGoogle Scholar
  32. White, K. L., Lysy, H. H., and Holsapple, M. P., Immunosuppression by polycyclic aromatic hydrocarbons: a structureactivity relationship in B6C3F1 and DBA/2 mice.Immunopharmacology, 9, 155–164 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2004

Authors and Affiliations

  • Nam Hee Kim
    • 1
  • Sun Hee Hyun
    • 1
  • Chun Hua Jin
    • 1
  • Sang Kyu Lee
    • 1
  • Dong Wook Lee
    • 1
  • Tae Won Jeon
    • 1
  • Jae Sung Lee
    • 2
  • Young Jin Chun
    • 3
  • Eung Seok Lee
    • 1
  • Tae Cheon Jeong
    • 1
  1. 1.College of PharmacyYeungnam UniversityKyungsanKorea
  2. 2.College of Natural ResourcesYeungnam UniversityKyungsanKorea
  3. 3.College of PharmacyChungang UniversitySeoulKorea

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