Skip to main content
Log in

Evaluation of activity of cytochrome P-450-dependent monooxygenase system induced by β-naphthoflavone and dexamethasone in rats at different ages

  • Published:
AGE Aims and scope Submit manuscript

Abstract

This study was undertaken to investigate the effects of age and some inducers (BNF-40 mg/kg/day, DEX − 20 mg/kg/day for 3 days each) on hepatic mixed function oxidase. Wistar male rats of very young (0.5 and 1 months), older (2, 4, 8,12 months) and very old (20 and 28 months) ages were used. The cytochrome P-450 content and the activity of NADH-cytochrome b5 reductase were highest in one-month-old animals, while the cytochrome b5 content was highest in the youngest but NADPH-cytochrome P-450 activity in the oldest rats. β-Naphthoflavone (BNF) treatment resulted in an enhanced content of cytochrome P-450 in all age groups but the activity NADPH-cytochrome P-450 reductase was increased only in the oldest rats. Dexamethasone (DEX) treatment led to a decrease in the activity of NADPH-cytochrome P-450 reductase in the oldest animals only. The cytochrome P-450 content was decreased in young animals (0.5-, 1-, 2-month-old), too. BNF and DEX decreased the cytochrome b 5 content and the activity of NADH-cytochrome b5 in all age groups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schmucker, D.L. and Lonergan, E.T.: Ageing and drug disposition. Rev. Biol. Res. Aging, 3: 509–535, 1987.

    CAS  Google Scholar 

  2. Stadtman, E.R.: Oxidation of proteins by mixed-function oxidation systems. Trends Biochem. Sci., 11: 11–12, 1986.

    Article  CAS  Google Scholar 

  3. Nebert, D.W., Adesnik, M., Coon, M.J., Estabrook, R.W., Gonzalez, F.J., Guengerich, F.P., Gunsalus, I.C., Johnson, E.F., Kemper, B., Levin, W., Philips, I.R., Sato, R., and Waterman, M.R.: The P450 gene super family. Recommended nomenclature. DNA, 6: 1–11, 1987.

    PubMed  CAS  Google Scholar 

  4. Nebert, D.W., Nelson, D.R., Coon, M.J., Estabrook, R.W., Feyereisen, R., Fujii-Kuriyama, Y., Gonzalez, F.J., Guengerich; F.P., Gunsalus, I.C., Johnson, E.F., Loper, J.C:, Sato, R., Waterman, M.R., and Waxman, D.J.: The P450 superfamily: Update on new sequences, gene mapping, and recommended nomenclature. DNA Cell. Biol., 10: 1–14, 1991.

    PubMed  CAS  Google Scholar 

  5. Lum, P.Y., Walkers, S., and Ioannides, C.: Foetal and neonatal development of cytochrome P-450 and cytochrome P-448 catalyzed mixed function oxidases in the rat: Induction by 3-methylcholanthrene. Toxicol., 35: 307–317, 1985.

    Article  CAS  Google Scholar 

  6. Sun, J., Lau, P.P., and Strobel, H.V.: Aging modifiers the expression of hepatic microsomal cytochromes P-450 after pretreatment of rats with β-naphthoflavone or phenobarbital. Exp. Gerontol., 21: 65–73, 1986.

    Article  PubMed  CAS  Google Scholar 

  7. Cresteil, T., Beaune, P., Celier, C., Leroux, J.P., and Guengerich, F.P.: Cytochrome P-450_isozyme content and monooxygenase activities in rat liver: Effect of ontogenesis and pretreatment by phenobarbital and 3-methylcholanthrene. J. Pharmacol. Exp. Ther., 236: 269–276, 1986.

    PubMed  CAS  Google Scholar 

  8. Vlasuk, G.P. and Waltz, Jr., F.G.: Liver microsomal polypeptides from Fischer-344 rats affected by age, sex and xenobiotics induction. Archiv. Biochem. Biophys., 214: 248–259, 1982.

    Article  CAS  Google Scholar 

  9. Kamataki, T., Yamazoe, Y., and Kato, R.: Alteration in the population of sex-specific P-450_species in rat liver microsomes during aging, in Liver and Aging, Kitani, K., Ed., Elsevier Science Pub., 1986, pp. 15–27.

  10. Leakey, J.EA.: Ontogenesis, in Biological Basis of Detoxication, edited by W.B. Jakoby and J. Caldwell, New York, Academic Press, 1983, pp. 77–103.

    Google Scholar 

  11. Devasayam, T.P.A., Pushpendran, Ch.K., and Eapen, J.: Changes in enzymes of hepatic rough and smooth microsomes during postnatal development and ageing of rats. Mech. Ageing Dev., 21: 365–375, 1983.

    Article  Google Scholar 

  12. Imaoka, S., Fujita, S., and Funae, Y.: Age-dependent expression of cytochrome P-450s in rat liver. Biochim. Biophys. Acta, 1097: 187–192, 1991.

    PubMed  CAS  Google Scholar 

  13. Kitani, K.: Neurohumoral control of liver functions during aging. Gerontol., 34: 55–63, 1988.

    Article  CAS  Google Scholar 

  14. Bitar, M.S. and Shapiro, B.H.: Aberration of heme and hemoprotein in aged female rats. Mech. Ageing Dev., 38: 189–197, 1987.

    Article  PubMed  CAS  Google Scholar 

  15. Kao, J. and Hudson, P.: Induction of the hepatic cytochrome P-450-dependent monooxygenase system in young and geriatric rats. Biochem. Pharmacol., 29:1191–1194, 1980.

    Article  PubMed  CAS  Google Scholar 

  16. Rikans, L.E. and Notley, B.A.: Age-related changes in hepatic microsomal drug metabolism are substrate selective. J. Pharmacol. Exp. Therap., 220: 574–578, 1982.

    CAS  Google Scholar 

  17. Vlasuk, G.P. and Walz Jr., F.G.: Liver microsomal polypeptides from Fischer-344 rats affected by age, sex and xenobiotics induction. Archiv. Biochem. Biophys., 214: 248–259, 1982.

    Article  CAS  Google Scholar 

  18. Rosenberg, D.W., Sardana, M.K., and Kappas, A.: Altered induction response of hepatic cytochrome P-450 to phenobarbital, 3-methylcholanthrene, and β-naphthoflavone in organtin-treated animals. Biochem. Pharmacol., 34: 997–1005, 1985.

    Article  PubMed  CAS  Google Scholar 

  19. Rikans, L.E., and Notley, B.A.: Differential effects of aging on hepatic microsomal monooxygenase induction by phenobarbital and β-naphthoflavone. Biochem. Pharmacol., 31: 2339–2343. 1982.

    Article  PubMed  CAS  Google Scholar 

  20. Wrighton, S.A. and Elswick, B.: Modulation of the induction of rat hepatic cytochromes P-450 by selenium deficiency. Biochem. Pharmacol., 38: 3767–3771, 1989.

    Article  PubMed  CAS  Google Scholar 

  21. Srivastava, G., Bawden, M.J., Hansen, A.J., and May, B.K.: Heme may not be a positive regulator of cytochrome P-450 gene expression. Eur. J. Biochem., 178: 689–692, 1989.

    Article  PubMed  CAS  Google Scholar 

  22. Schuetz, E.G., Hazelton, G.A., Hall, J., Watkins, P.B., Klaasen, C.D., and Guzelian, P.S.: Induction of digitoxigenin monodigitoxoside UDP-glucuronosyltransferase activity by glucocorticoids and other inducers of cytochrome P-450p in primary monolayer cultures of adult rat hepatocytes and in human liver. J. Biol. Chem., 261: 82707–8275, 1986.

    Google Scholar 

  23. Decker C., Sugiyama, K., Underwood, M., and Correia, M.A.: Inactivation of rat hepatic cytochrome P-450 by spironolactone. Biochem. Biophys. Res. Commun., 136: 1162–1169, 1986.

    Article  PubMed  CAS  Google Scholar 

  24. Antignac, E. and Fukuhara, M.: Identification of a constitutive form of cytochrome P-450_with high activity towards macrolide antibiotics in Syrian golden hamster liver. Res. Commun. Chem. Pathol. Pharm., 76: 43–51, 1992.

    CAS  Google Scholar 

  25. Birnbaum, LS. and Baird, M.B.: Induction of hepatic mixed function oxidases in senescent rodents. Exp. Gerontol., 13: 299–303, 1978.

    Article  PubMed  CAS  Google Scholar 

  26. Birnbaum, L.S.: Altered hepatic drug metabolism in senescent mice. Exp. Gerontol., 15: 259–267, 1980.

    Article  PubMed  CAS  Google Scholar 

  27. Hlavica, P.: On the function of cytochrome b5 in the cytochrome P-450 dependent oxygenase system. Archiv. Biochem. Biophys., 228: 600–608, 1984.

    Article  CAS  Google Scholar 

  28. Czekaj, P., Plewka, A., Kaminski, M., Nowaczyk-Dura, G., Pawlicki, K., and Wielgus-Serafinska, E.: Daily and circadian rhythms in the activity of mixed function oxidases system in rats of different age. Biol. Rhythm Res., 25: 67–75, 1994.

    Article  CAS  Google Scholar 

  29. Dallner, G,: Isolation of rough and smooth microsomes–general. Methods Enzymol., 32: 191–215, 1974

    Google Scholar 

  30. Estabrook, R.W. and Werringloer, J.: The measurement of different spectra: Application to the cytochromes of microsomes. Methods Enzymol., 52: 212–220, 1978.

    PubMed  CAS  Google Scholar 

  31. Hodges, T.K.and Leonard, R.T.: Purification of a plasma membrane-bound adenosine triphosphatase from plant roots. Methods Enzymol., 32: 392–406, 1974.

    Article  PubMed  CAS  Google Scholar 

  32. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randal, R.J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193: 265–275, 1951.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work is part five of a series of papers: (1) A. Plewka, M. Bienioszek, Arch. Toxicol., 68:32–36 (1994); (2) A. Plewka, Arch. Gerontol. Ger. 20:149–158 (1995); (3) A. Plewka, M. Bienioszek, D. Plewka, Mech. Ageing Dev., 74:79–88 (1994); (4) A. Plewka, M. Kaminski, D. Plewka, Exp. Gerontol. (submitted).

About this article

Cite this article

Plewka, A., Plewka, D. Evaluation of activity of cytochrome P-450-dependent monooxygenase system induced by β-naphthoflavone and dexamethasone in rats at different ages. AGE 18, 159–165 (1995). https://doi.org/10.1007/BF02432630

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02432630

Keywords

Navigation