, Volume 157, Issue 1, pp 209–217 | Cite as

Pulmonary accumulation of drugs in vitamin a deficiency

  • Zahid H. Siddik
  • Michael A. Trush
  • Theodore E. Gram


The effect of vitamin A deficiency on the uptake of several drug substrates in rat lung slices was determined. Vitamin A deficiency resulted in significant increases in the pulmonary accumulation of imipramine, chlorpromazine, 5-hydroxytryptamine and norepinephrine. The enhanced uptake of 5-hydroxytryptamine by deficient slices was probably due to a decrease in pulmonary monoamine oxidase (MAO) activity, since accumulation of this amine was similar in control and deficient slices that had been preincubated in pargyline, an inhibitor of MAO. In contrast, pulmonary uptake of methadone and paraquat was not affected in vitamin A deficiency. These results suggest that the enhanced susceptibility of the respiratory tract of vitamin A deficient animals to toxic chemicals may be due in part to an increase in the accumulation of the chemicals by the lung.

Key words

Vitamin A deficiency Lung Drug accumulation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anderson MW, Philpot RM, Bend JR, Wilson AGE, Eling TE (1977) Pulmonary uptake and metabolism of chemicals by the lung. In: Clinical Toxicology, Vol. 18, p. 85. Duncan WAM, Leonard BJ (eds) Amsterdam-Oxford, Excerpta MedicaGoogle Scholar
  2. 2.
    Baginski ES, Foà PP, Zak B (1967) Microdetermination of inorganic phosphate, phospholipids, and total phosphate in biologic materials. Clin Chem 13:326–332PubMedGoogle Scholar
  3. 3.
    Becking GC (1973) Vitamin A status and hepatic drug metabolism in the rat. Can J Physiol Pharmacol 51:6–11PubMedGoogle Scholar
  4. 4.
    Bickel MH (1975) Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components. J Pharm Pharmacol Pharmac 27:733–738Google Scholar
  5. 5.
    Bjelke E (1975) Dietary vitamin A and human lung cancer. Int J Cancer 15:561–565PubMedCrossRefGoogle Scholar
  6. 6.
    Bornstein WA, Lamden MP, Chuang AHL, Gross RL, Newberne PM, Bresnick E (1978) Inability of vitamin A deficiency to alter benzo(a)pyrene metabolism in Syrian hamsters. Cancer Res 38:1497–1501PubMedGoogle Scholar
  7. 7.
    Boyd MR (1977) Evidence for the Clara cell as a site of cytochrome P450-dependent mixed-function oxidase activity in lung. Nature (London) 269:713–715CrossRefGoogle Scholar
  8. 8.
    Chen PS, Toribara TY, Warner H (1956) Microdetermination of phosphorus. Anal Chem 28:1756–1758CrossRefGoogle Scholar
  9. 9.
    Chhabra RS, Miranda CL, Bend JR, Mukhtar H, Zeiger E (1977) Effects of vitamin A deficiency (A-def) on extrahepatic drug metabolism in the guinea pig and rabbit. Pharmacologist 19:160Google Scholar
  10. 10.
    Colby HD, Kramer RE, Greiner JW, Robinson DA, Krause RF, Canady WJ (1975) Hepatic drug metabolism in retinol-deficient rats. Biochem Pharmacol 24:1644–1646CrossRefGoogle Scholar
  11. 11.
    Di Francesco C, Bickel MH (1977) Membrane lipids as intracellular binders of chlorpromazine and related drugs. Chem Biol Inter 16:335–346CrossRefGoogle Scholar
  12. 12.
    Drew R, Siddik ZH, Gram TE (1979) Uptake and efflux of14C-paraquat by rat lung slices: The effect of imipramine and other drugs. Toxicol Appl Pharmacol 49:473–478PubMedCrossRefGoogle Scholar
  13. 13.
    Dugan RE, Frigerio NA, Siebert JM (1964) Colorimetric determination of vitamin A and its derivatives with trifluoroacetic acid. Anal Chem 36:114–117CrossRefGoogle Scholar
  14. 14.
    Folch J, Less M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509PubMedGoogle Scholar
  15. 15.
    Genta VM, Kaufman DG, Harris CC, Smith JM, Sporn MB, Saffiotti U (1974) Vitamin A deficiency enhances binding of benzo(a)pyrene to tracheal epithelial DNA. Nature (London) 247:48–49CrossRefGoogle Scholar
  16. 16.
    Gillis CN, Roth JA (1976) Pulmonary disposition of circulating vasoactive hormones. Biochem Pharmacol 25:2547–2553PubMedCrossRefGoogle Scholar
  17. 17.
    Grover PL (1974) K-region epoxides of polycyclic hydrocarbons: Formation and further metabolism by rat lung preparations. Biochem Pharmacol 23:333–343PubMedCrossRefGoogle Scholar
  18. 18.
    Higginson J (1977) The role of the pathologist in environmental medicine and public health. Am J Pathol 86:460–484PubMedGoogle Scholar
  19. 19.
    Junod AF (1975) Mechanisms of drug accumulation in the lung. In: Lung Metabolism, p. 219. Junod AF, de Haller R (eds). New York, Academic PressGoogle Scholar
  20. 20.
    Junod AF (1975) Mechanisms of uptake of biogenic amines in the pulmonary circulation. In: Lung Metabolism, p. 387. Junod AF, de Haller R (eds). New York, Academic PressGoogle Scholar
  21. 21.
    Lakowicz JR, Hylden JL (1978) Asbestos-mediated membrane uptake of benzo(a)pyrene observed by fluorescence spectroscopy. Nature (London) 275:446–448CrossRefGoogle Scholar
  22. 22.
    Lowry OH, Rosebrough NG, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  23. 23.
    Lucy JA (1969) Some possible roles for vitamin A in membranes: Micelle formation and electron transfer. Am J Clin Nutr 22:1033–1044PubMedGoogle Scholar
  24. 24.
    Lucy JA, Dingle JT (1964) Fat-soluble vitamins and biological membranes. Nature (London) 204:156–160CrossRefGoogle Scholar
  25. 25.
    Philpot RM, Anderson MW, Eling TE (1977) Uptake, accumulation and metabolism of chemicals by the lung. In: Lung Biology in Health and Disease: Metabolic Functions of the Lung, Vol. 4, p. 123. Bakhle YS, Vane JR (eds). New York and Basel, Marcel DekkerGoogle Scholar
  26. 26.
    Roels OA, Anderson OR, Lui NST, Shah DO, Trout ME (1969) Vitamin A and membranes. Am J Clin Nutr 22:1020–1032PubMedGoogle Scholar
  27. 27.
    Rose MS, Smith LL, Wyatt I (1974) Evidence for energy-dependent accumulation of paraquat into rat lung. Nature (London) 252:314–315CrossRefGoogle Scholar
  28. 28.
    Sauberlich HE, Hodges RE, Wallace DL, Kolder H, Canham JE, Hood J, Raica JrN, Lowry LK (1974) Vitamin A metabolism and requirements in the human studied with the use of labeled retinol. Vitam Horm 32:251–275PubMedCrossRefGoogle Scholar
  29. 29.
    Sporn MB, Dunlop NM, Newton DL, Smith JM (1976) Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 35:1332–1338PubMedGoogle Scholar
  30. 30.
    Yonemoto T, Oh M (1969) On the functional site of vitamin A. J Vitaminol 15:254–260Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Zahid H. Siddik
    • 1
  • Michael A. Trush
    • 1
  • Theodore E. Gram
    • 1
  1. 1.Laboratory of ToxicologyNational Cancer Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations