Long-term administration of high dose vitamin A to rats does not cause fetal malformations: Macroscopic, skeletal and physicochemical findings

Journal of Nutrition

Volumn 126, Issue 4, 1996, Pages 973-983

  Biesalski, Hans K ^a   Hemmes, Christian ^a   El Hanafy, Magdy ^a   Weiser, Harald ^b   Zschaebitz, Horst ^c   Stofft, Eckart ^c  

^a UNIVERSITY OF HOHENHEIM   (Germany)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

^c JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

rats; retinoic acid; retinyl esters; teratogenicity; vitamin A

Indexed keywords

RETINOIC ACID; RETINOL; RETINOL ESTER;

ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG MEGADOSE; FEMALE; FETUS; FETUS LIVER; FETUS MALFORMATION; LONG TERM EXPOSURE; MOTHER FETUS RELATIONSHIP; NONHUMAN; ORAL DRUG ADMINISTRATION; PLACENTAL TRANSFER; RAT; TERATOGENICITY; VITAMIN BLOOD LEVEL; VITAMIN INTAKE;

EID: 0029876496     PISSN: 00223166     EISSN: None     Source Type: Journal    
DOI: 10.1093/jn/126.4.973     Document Type: Article

References (44)

1. Armstrong, R. B., Ashenfelter, K. O., Eckhoff, C., Levin, A. A. & Shapiro, S. S. (1994) General and reproductive toxicology of retinoids. In: The Retinoids: Biology, Chemistry and Medicine (Sporn, M. B., Roberts, A. B. & Goodman, D. S., eds.), 2nd ed., pp 545-572. Raven Press, New York, NY.
2. 3H) retinoic acid after an oral dose in rats. Biochem. J. 277: 527-531.
3. Biesalski, H. K. (1989a) Comparative assessment of the toxicology of vitamin A and retinoic acid. Toxicology 27: 117-161.
4. Biesalski, H. K. (1990a) Separation of retinyl esters and their geometric isomers by isocratic adsorption high-performance liquid chromatography. In: Methods in Enzymology (Packer, L., ed.), 189: 83-91. Academic Press, San Diego, CA.
5. Biesalski, H. K. (1990b) Isocratic adsorption HPLC of trace amounts of retinyl esters with a closed recycling system. Micronutrient Analysis 7: 97-116.
6. Biesalski, H. K., Gabbert, H. E., Gerharz, C. D., Engers, R. & Brodda, K. (1989) Uptake and metabolism of retinoic acid induces inhibition of cell growth: a study in a rat rhabdomyosarcoma cell line (BA-HAN-1C) using non-molecular theoretical models. Int. J. Vit. Nutr. Res. 60: 6-17.
7. Biesalski, H. K. & Doepner, G. (1992) All-trans retinyl- and all-trans retinoyl-β-D-glucuronides: synthesis, pharmacology and biological activity. In: Progress in Retinoids (Livrea, M. & Packer, L., eds.), pp. 329-339. Marcel Dekker, New York, NY.
8. Biesalski, H. K. (1993) Bioavailability of inhalative application of vitamin A. Comparison of intramuscular and oral administration. In: Proceedings of the international Conference Bioavailability '93, Ettlingen, Germany, May 9-13. (U. Schlemmer, ed.), pp. 336-346.
9. Biesalski, H. K., Doepner, G., Kunz, H., Paust, J. & John, M. (1995) Convenient synthesis of biologically important retinoids. Liebigs Ann. 717-720.
10. Blomhoff, R., Green, M. & Norum, K. (1992) Vitamin A: physiological and biochemical processing. Annu. Rev. Nutr. 12: 37-57.
11. Boylan, J. F. & Gudas, L. (1991) Overexpression of the cellular retinoic acid binding protein I (CRABP I) in a reduction in differentiation-specific gene expression in F9 teratocarcinoma cells. J. Cell Biol. 112: 965-979.
12. Cavalli-Sforza, L. (1964) Grundbegriffe der Biometrie, insbesondere der statistischen Methoden bei der Wertbemessung biologisch wirksamer Substanzen. Seiten 69-80. Gustav Fischer Verlag, Stuttgart, Germany.
13. Collins, M. D., Tzirnas, G., Hummler, H., Bürgin, H. & Nau, H. (1994) Comparative teratology and transplacental pharmacokinetics of all-trans retinoic acid, 13-cis retinoic acid and retinyl palmitate following daily administrations in rats. Toxicol. Appl. Pharmacol. 127: 132-144.
14. Eckhoff, Ch., Lofberg, B., Chahoud, I. & Nau, H. (1989) Transplacental pharmacokinetics and teratogenicity of a single dose of retinol (vitamin A) during organogenesis in the mouse. Toxicol. Lett. 48: 171-184.
15. Eckhoff, Ch. & Nau, H. (1990a) Identification and quantitation of all-trans retinoic acid and 13-cis-4-oxo-retinoic acid in human plasma. J. Lipid. Res. 31: 1445-1454.
16. Eckhoff, Ch. & Nau, H. (1990b) Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis. Arch. Toxicol. 64: 502-503.
17. Eckhoff, Ch., Bailey, J. R., Collins, M. D., Slikker, W., Jr. & Nau, H. (1991a) Influence of dose and pharmaceutical formulation of vitamin A on plasma levels of retinyl esters and retinol and metabolic generation of retinoic acid compounds and β-glucuronides in the cynomolgus monkey. Toxicol. Appl. Pharmacol. 111: 116-127.
18. Eckhoff, Ch. (1991b) Untersuchungen zur Bedeutung des Metabolismus von Retinol für den Mechanismus der teratogenen Wirkung von hochdosiertem Vitamin A bei Maus, Affe, Mensch. Thesis Berlin.
19. Food and Nutrition Board, National Research Council (1989) Recommended Dietary Allowances, 10 th ed., pp 78-92. National Academy Press. Washington, D.C.
20. Friedrich, W. (1987) Handbuch der Vitamine, pp 69-71. Urban & Schwarzenberg, München, Wien, Baltimore.
21. Gerlach, T., Biesalski, H. K. & Baessler, K. H. (1988) Serum Vitamin A-Bestimmungen und ihre Aussagekraft zum Vitamin A-Status. Z. Ernäh-rungswiss. 27: 57-70.
22. Gerlach, T., Biesalski, H. K., Weiser, H., Haeussermann, B. & Baessler, K. H. (1989) Vitamin A in parenteral nutrition: uptake and distribution of retinyl esters after intravenous application. Am. J. Clin. Nutr. 50: 1029-1038.
23. Gunning, D. B., Barua, A. B. & Olson, J. A. (1993) Comparative teratogenicity and metabolism of all-trans retinoic acid, all-trans retinoyl β-glucose, and all-trans retinoyl β-glucuronide in pregnant Sprague-Dawley rats. Teratology 47: 29-36.
24. Lampron, C., Rochette-Egly, C., Gorry, P., Dollé, P., Mark, M., Le-Meur, M. & Chambon, P. (1995) Mice deficient in cellular retinoic acid binding protein II (CRABP II) or in both CRABP I and CRABP II are essentially normal. Development 121: 539-548.
25. McCormick, A. M., Napoli, J. L., Schnoes, H. K. & DeLuca, H. F. (1978) Isolation and identification of 5,6-epoxy retinoic acid: a biologically active metabolite of retinoic acid. Biochemistry 17: 4085-4090.
26. McCormick, A. M. & Napoli, J. L. (1982) Identification of 5,6-epoxy retinoic acid as an endogenous retinol metabolite. J. Biol. Chem. 257: 1730-1735.
27. Means, A. L. & Gudas, L. J. (1995) The roles of retinoids in vertebrate development. Annu. Rev. Biochem. 64: 201-233.
28. Morriss-Kay, G. (1992) Retinoic acid and Development. Pathobiology 60: 264-270.
29. Nolen, G. A. (1989) Effect of high systemic background level of vitamin A on the teratogenicity of all-trans retinoic acid given either acutely or subacutely. Teratology 39: 333-339.
30. Pacifici, M., Cossu, G., Molinaro, M. & Tato, F. (1980) Vitamin A inhibits chondrogenesis but not myogenesis. Exp. Cell. Res. 129: 469-474.
31. Peiker, G., Eckhoff, C., Nau, H. & Michels, W. (1993) Untersuchungen über Plasmaspiegel und Metabolismus von Vitamin A bei Frauen im fertilen Alter und dessen Bedeutung. In: Vitamine und weitere Zusatzstoffe bei Mensch und Tier. 4. Symposium 30.9.-1.10.1993 in Jena/Thüringen (Flachowsky, G. & Schubert, R., Hsg.), Seiten 22-30. Wissenschaftl. Fachverlag Dr. Fleck, Niederkleen, Germany.
32. Pillans, P. I. & Ponzi, P. I. (1988) The effects of in vivo administration of teratogenic doses of vitamin A during the preimplantation in the mouse. Teratology 37: 7-11.
33. Public Affairs Committee of the Teratology Society (1987) Teratology Society Position Paper: Recommendations for vitamin A use during pregnancy. Teratology 35: 269-275.
34. Ramp, U., Gerharz, C. D., Eifler, E., Biesalski, H. K. & Gabbert, H. E. (1994) Effects of retinoic acid metabolites on proliferation and differentiation of the clonal rhabdomyosarcoma cell line BA-HAN-1C. Biol. Cell. 81: 31-37.
35. Rosa, F. W., Wilk, A. L. & Kelsey, F. O. (1986) Vitamin congeners. Teratology 33: 355-362.
36. Smith, F. R. & Goodman, D. S. (1976) Vitamin A transport in human vitamin A toxicity. N. Engl. J. Med. 294: 805-808.
37. Snedecor, G. W. & Cochran, W. G. (1982) Statistical Methods, 7th ed., pp. 141-144. The Iowa State University Press, Ames, IA.
38. Staples, R. E. & Schnell, V. L. (1964) Refinements in rapid clearing technic in the KOH-alizarin red S. Method for fetal bone. Stain Tech. 39: 61-63.
39. Underwood, B. A. (1989) Teratogenicity of vitamin A. In: Elevated Dosages of Vitamins. Benefits and Hazards. (Walter, P., Brubacher, G. & Staehelin, H., eds.), pp. 43-55. Hans Huber Publ., Bern, Stuttgart, Wien.
40. Weiser, H. & Vecchi, M. (1981) Stereoisomers of -tocopheryl acetate, characterisation of the sample by physico-chemical methods and determination of biological activities in the rat resorption-gestation test. Int. J. Vit. Nutr. Res. 51: 100-113.
41. Weiser, H., Probst, H. P. & Bachmann, H. (1991) Verminderung der Nebenwirkungen hoher Vitamin-A-Dosen durch ein ausgewogenes Vitamin-A- und E-Angebot. In: Vitamine und Zusatzstoffe bei Mensch und Tier. 3. Symposium 26./27. 9. 1991, Stadtroda bei Jena/Thüringen (Flachowsky, G., Schöne, F. & Hennig, A. Hsg,), Seiten 84-89. Wissenschaftl. Verlag Dr. Fleck, Niederkleen, Germany.
42. Weiser, H., Probst, H. P. & Bachmann, H. (1992) Vitamin E prevents side effects of high doses of vitamin A in chicks. Ann. N. Y. Acad. Sci. 669: 396-398.
43. Wellner, U. & Biesalski, H. K. (1985) Computerized interpretation of HPLC chromatograms by absorbance ratio method and derivative spectroscopy. Lecture Notes. In: Med. Inf. 25: 579-583.
44. Wilson, J. G. (1965) Embryological considerations in teratology. In: Teratology, Principles and Techniques (Wilson, J. G. & Warkany, J., eds.), pp. 251-261. Univ. of Chicago.