Effect of a high systemic background level of vitamin A on the teratogenicity of all-trans-retinoic acid given either acutely or subacutely.
Groups of 12 Charles River CD virgin female rats were either supplemented with 25,000 IU/kg of vitamin A palmitate or not during the first 8 days of pregnancy and in the first experiment given a single dose of either 5 or 10 mg/kg of all-trans-retinoic acid (RA) on day 9 of pregnancy. In a second experiment, similar groups were given either 4 or 8 mg/kg RA daily from day 6 through day 15 so that each treatment with RA was given to vitamin A supplemented rats or nonsupplemented rats. The high systemic background of vitamin A increased the teratogenicity of the 10 mg/kg dose of RA given on day 9 by 50%, but reduced the teratogenicity of the 8 mg/kg dose given on days 6-15. The reasons for this paradox are discussed and related to the human propensity to self-medicate with megadoses of vitamins.
Nolen
G A
GA
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D009024:Morphogenesis / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013723:Teratogens / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism / Q000633:toxicity*; D014801:Vitamin A / Q000097:blood*
D013723:Teratogens; D014801:Vitamin A; D014212:Tretinoin