Embryotoxic doses of vitamin A to rabbits result in low plasma but high embryonic concentrations of all-trans-retinoic acid: Risk of vitamin A exposure in humans

Journal of Nutrition

Volumn 126, Issue 9, 1996, Pages 2159-2171

  Tzimas, Georg ^a   Collins, Michael D ^b   Bürgin, Heinrich ^c   Hummler, Hans ^c   Nau, Heinz ^a  

^a FREIE UNIVERSITÄT BERLIN   (Germany)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

embryotoxicity; rabbits; retinoic acid; retinol; vitamin A

Indexed keywords

RETINOIC ACID; RETINOL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONCENTRATION RESPONSE; DRUG MEGADOSE; EMBRYOTOXICITY; NONHUMAN; RABBIT; RISK ASSESSMENT; TERATOGENICITY; VITAMIN BLOOD LEVEL; VITAMIN INTAKE;

ANIMALIA; ORYCTOLAGUS CUNICULUS;

EID: 0029829114     PISSN: 00223166     EISSN: None     Source Type: Journal    
DOI: 10.1093/jn/126.9.2159     Document Type: Article

References (33)

1. Agnish, N. D. & Kochhar, D. M. (1993) Developmental toxicity of retinoids. In: Retinoids in Clinical Practice. The Risk-Benefit Ratio (Koren, G., ed.), pp. 47-76. Marcel Dekker, New York, NY.
2. Allenby, G., Bocqeul, M.-T., Saunders, M., Kazmer, S., Speck, J., Rosenberger, M., Lovey, A., Kastner, P., Grippo, J. F., Chambon, P. & Levin, A. A. (1993) Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoids. Proc. Natl. Acad. Sci. U.S.A. 90: 30-34.
3. Arnhold, T., Tzimas, G., Wittfoht, W., Plonait, S. & Nau, H. (1996) Identification of 9-cis-retinoic acid, 9,13-di-cis-retinoic acid, and 14-hydroxy-4,14-retro-retinol in human plasma after liver consumption. Life Sci. (in press).
4. Bollag, W. & Holdener, E. E. (1992) Retinoids in cancer prevention and therapy. Ann. Oncol. 3: 513-526.
5. Buss, N. E., Tembe, E. A., Prendergast, B. D., Renwick, A. G. & George, C. F. (1994) The teratogenic metabolites of vitamin A in women following supplements and liver. Hum. Exp. Toxicol. 13: 33-43.
6. Chen, H., Namkung, M. J. & Juchau, M. R. (1995) Biotransformation of all-trans-retinol and all-trans-retinal to all-trans-retinoic acid in rat conceptal homogenates. Biochem. Pharmacol. 50: 1257-1264.
7. Collins, M. D., Eckhoff, C., Chahoud, I., Bochert, G. & Nau, H. (1992) 4-Methylpyrazole partially ameliorated the teratogenicity of retinol and reduced the metabolic formation of all-trans-retinoic acid in the mouse. Arch. Toxicol. 66: 652-659.
8. Collins, M. D., Tzimas, G., Hummler, H., Bürgin, H. & Nau, H. (1994) Comparative teratology and pharmacokinetics of all-trans-retinoic acid, 13-cis-retinoic acid, and retinyl palmitate in the rat following daily administrations of equipotent teratogenic doses. Toxicol. Appl. Pharmacol. 127: 132-144.
9. Creech Kraft, J., Schuh, T., Juchau, M. R. & Kimelman, D. (1994) Temporal distribution, localization and metabolism of all-trans-retinol, didehydroretinol and all-trans-retinal during Xenopus development. Biochem. J. 301: 111-119.
10. Creech Kraft, J., Shepard, T. & Juchau, M. R. (1993) Tissue levels of retinoids in human embryos/fetuses. Reprod. Toxicol. 7: 11-15.
11. Eckhoff, C., Collins, M. D. & Nau, H. (1991a) Human plasma all-trans-, 13-cis- and 13-cis-4-oxoretinoic acid profiles during subchronic vitamin A supplementation: comparison to retinol and retinyl ester plasma levels. J. Nutr. 121: 1016-1025.
12. Eckhoff, C., Bailey, J. R., Collins, M. D., Slikker, W., Jr. & Nau, H. (1991b) 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.
13. Eckhoff, C., Löfberg, B., Chahoud, I., Bochert, G. & 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.
14. Eckhoff, C. & Nau, H. (1990) Identification and quantification of all-trans- and 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid in human plasma. J. Lipid Res. 31: 1445-1454.
15. Gudas, L. J. (1994) Retinoids and vertebrate development. J. Biol. Chem. 269: 15399-15402.
16. Gudas, L. J., Sporn, M. B. & Roberts, A. B. (1994) Cellular biology and biochemistry of retinoids. In: The Retinoids: Biology, Chemistry, and Medicine (Sporn, M. B., Roberts, A. B. & Goodman, D. S., eds), pp. 443-520. Raven Press, New York, NY.
17. Horst, R. L., Reinhardt, T. A., Goff, J. P., Koszewski, N. J. & Napoli, J. L. (1995b) 9,13-Di-cis-retinoic acid is the major circulating geometric isomer of retinoic acid in the periparturient period. Arch. Biochem. Bioph. 322: 235-239.
18. Horst, R. L., Reinhardt, T. A., Goff, J. P., Nonnecke, B. J. Gambhir, V. K., Fiorella, P. D. & Napoli, J. L. (1995a) Identification of 9-cis-, 13-cis-retinoic acid as a major circulating retinoid in plasma. Biochemistry 34: 1203-1209.
19. Kamm, J. J. (1982) Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids. J. Am. Acad. Dermatol. 6: 652-659.
20. Napoli, J. L., Posch, K. P., Fiorella, P. D. & Boerman, M.H.E.M. (1991) Physiological occurrence, biosynthesis and metabolism of retinoic acid: evidence for roles of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the pathway of retinoic acid homeostasis. Biomed. Pharmacother. 45: 131-143.
21. Nau, H., Chahoud, I., Dencker, L., Lammer, E. J. & Scott, W. J. (1994) Teratogenicity of vitamin A and retinoids. In: Vitamin A in Health and Disease (Blomhoff, R., ed.), pp. 615-663. Marcel Dekker, New York, NY.
22. Pijnappel, W. W. M., Hendriks, H. F. J., Folkers, G. E., van den Brink, C. E., Dekker, E. J., Edelenbosch, C., van der Saag, P. T. & Durston, A. J. (1993) The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification. Nature (Lond.) 366: 340-344.
23. Rosa, F. W. (1993) Retinoid embryopathy in humans. In: Retinoids in Clinical Practice. The Risk-Benefit Ratio (Koren, G., ed.), pp. 77-109. Marcel Dekker, New York, NY.
24. Rothman, K. J., Moore, L. L., Singer, M. R., Nguyen, U. D. T., Mannino, S. & Milunsky, A. (1995) Teratogenicity of high vitamin A intake. N. Engl. J. Med. 333: 1369-1373.
25. Sass, J. O. & Nau, H. (1994) Single-run analysis of isomers of retinoyl-β-D-glucuronide and retinoic acid by reversed-phase high-performance liquid chromatography. J. Chromatogr. A 685: 182-188.
26. Scott, W. J., Jr., Walter, R., Tzimas, G., Sass, J. O., Nau, H. & Collins, M. D. (1994) Endogenous status of retinoids and their cytosolic binding proteins in limb buds of chick vs mouse embryos. Dev. Biol. 165: 397-409.
27. Thaller, C. & Eichele, G. (1990) Isolation of 3,4-didehydroretinoic acid, a novel morphogenetic signal in the chick wing bud. Nature (Lond.) 345: 815-819.
28. Törmä, H., Asselineau, D., Andersson, E., Martin, B., Reinicke, P., Chambon, P., Shroot, B., Darmon, M. & Vahlquist, A. (1994) Biologic activities of retinoic acid and 3,4-didehydroretinoic acid in human keratinocytes are similar and correlate with receptor affinities and transactivation properties. J. Invest. Dermatol. 102: 49-54.
29. Tzimas, G., Bürgin, H., Collins, M. D., Hummler, H. & Nau, H. (1994b) The high sensitivity of the rabbit to the teratogenic effects of 13-cis-retinoic acid is a consequence of prolonged exposure of the embryo to 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid, and not to all-trans-retinoic acid. Arch. Toxicol. 68: 119-128.
30. Tzimas, G., Sass, J. O., Wittfoht, W., Elmazar, M. M. A., Ehlers, K. & Nau, H. (1994a) Identification of 9,13-dicis-retinoic acid as a major plasma metabolite of 9-cis-retinoic acid and limited placental transfer of 9-cis-retinoic acid and 9,13-dicis-retinoic acid to the mouse and rat embryos. Drug Metab. Dispos. 22: 928-936.
31. Tzimas, G., Collins, M. D. & Nau, H. (1995) Developmental stage-associated differences in the transplacental distribution of 13-cis-and all-trans-retinoic acid as well as their glucuronides in rats and mice. Toxicol. Appl. Pharmacol. 133: 91-101.
32. Werler, M. W., Lammer, E. J., Rosenberg, L. & Mitchell, A. A. (1990) Maternal vitamin A supplementation in relation to selected birth defects. Teratology 42: 497-503.
33. Yen, A., Powers, V. & Fishbaugh, J. (1986) Retinoic acid induced HL-60 myeloid differentiation: dependence of early and late events on isomeric structure. Leuk. Res. 10: 619-629.