Prevention of vitamin A teratogenesis by phytol or phytanic acid results from reduced metabolism of retinol to the teratogenic metabolite, all-trans-retinoic acid
| Autor: | Thomas Arnhold, Mohamed M. Elmazar, Heinz Nau |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Vitamin
medicine.medical_specialty animal structures Phytanic acid medicine.drug_class Metabolite Retinoic acid Administration Oral Mice Inbred Strains Tretinoin Biology Toxicology Phytol chemistry.chemical_compound Mice Pregnancy Internal medicine medicine Animals Retinoid Vitamin A Chromatography High Pressure Liquid Retinol Abnormalities Drug-Induced Drug Synergism Metabolism Phytanic Acid Endocrinology Teratogens chemistry Prenatal Exposure Delayed Effects embryonic structures Female |
| Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology. 66(2) |
| ISSN: | 1096-6080 |
| Popis: | Previous studies in our laboratory showed a synergistic interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in regard to teratogenic effects produced in mice (M. M. Elmazar et al., 2001, TOXICOL: Appl. Pharmacol. 170, 2-9). In the present study the influence of phytol and phytanic acid (a RXR-selective ligand) on the teratogenicity of retinol and the RAR-selective ligand all-trans-retinoic acid was investigated by coadministration experiments on day 8.25 of gestation in NMRI mice. Phytol and phytanic acid, noneffective when administered alone, did not potentiate the teratogenicity induced by retinol or all-trans-retinoic acid. On the contrary, phytol and phytanic acid greatly reduced retinol-induced teratogenic effects (ear anotia, tail defects, exencephaly). The effect of phytol on all-trans-retinoic acid teratogenesis was limited (only resorptions and tail defects were reduced). Pharmacokinetic studies in nonpregnant animals revealed that phytol coadministration with retinol reduced plasma levels of retinol and retinyl esters, and drastically reduced the levels of the teratogenic retinol metabolite, all-trans-retinoic acid. Phytanic acid also reduced the oxidative metabolism and teratogenic effects of retinol. These results indicate that phytol and phytanic acid did not synergize with retinol and all-trans-retinoic acid in our mouse teratogenesis model. Instead, phytol and phytanic acid effectively blocked the teratogenic effects of retinol by drastically reducing the metabolic production of all-trans-retinoic acid. Phytol and phytanic acid may be useful for the prevention of vitamin A teratogenicity. |
| Databáze: | OpenAIRE |
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