Antisterility and Antivitamin K Activity of d-α-Tocopheryl Hydroquinone in the Vitamin E-deficient Female Rat

Daily administration of 5 mg of d-α-tocopheryl hydroquinone (ATHQ), intravenously or intraperitoneally throughout gestation, has been said to prevent fetal resorption in four out of five vitamin E-deficient rats (J. Nutr. 72, 322–324). These observations are supported by our bioassay tests involving 58 and 22 vitamin E-deficient rats given oral supplements of ATHQ and of d-α-tocopheryl acetate, respectively, over days 5 to 8 of gestation. Evidence presented suggested a minimal protective dose of approximately 50 mg of ATHQ, which, if distributed over the first 10 days of gestation, would represent about 5 mg/day. Evidence is presented that vitamin E fed after day 10 has little or no effect upon the course of gestation. In other experiments, daily doses of 125/mg/kg/day of ATHQ during early gestation in E-deficient rats caused excessive uterovaginal bleeding, intrauterine hemorrhage, and retarded development and death of fetuses. This represented a rather small margin between beneficial and detrimental effects of ATHQ. In male rats given 330/mg/kg/day of ATHQ the testis, epididymis and related fat body were particularly prone to hemorrhage. Because internal hemorrhages in both sexes were prevented by menaquinone, the phenomena observed were attributed to an induced deficiency of vitamin K through unknown actions of ATHQ.