{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T22:57:15Z","timestamp":1785711435842,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,5,19]],"date-time":"2005-05-19T00:00:00Z","timestamp":1116460800000},"content-version":"vor","delay-in-days":8692,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1981,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydroxyurea (HU) is a potent teratogen which caused 100% embryotoxic effects in New Zealand white rabbits when injected sc on gestational day 12. These included a high percentage of resorptions and severe craniofacial, trunk and limb deformities of all survivors. Co\u2010treatment of pregnant animals with the phenolic antioxidant propyl gallate (PG) resulted in amelioration of the embryotoxicity. Various amounts of PG (362\u2013906 mg\/kg) and HU (600\u2013750 mg\/ kg) were either injected simultaneously or mixed together for periods of time up to 45 min. The extent of amelioration was dependent upon the amount of PG, although the highest dose of PG caused maternal toxicity. Simultaneous injections of HU and PG were not as efficacious as mixture of the two chemicals prior to injection. The length of time which the HU and PG mixture was allowed to stand prior to injection had no effect on the extent of amelioration. The protective action of PG resulted in significant linear reductions in both resorptions and specific malformations with increasing doses of PG. Histologic analysis of HU and HU\u2010PG embryos disclosed that HU produced rapid cell death in the mesenchymal compartment of the embryo, particularly in the limb\u2010buds, beginning at 2 h after treatment. Cell debris increased in amount until 8 h and remained extensive at 16 h. In contrast, HU\u2010PG delayed the onset for cell death until 8 h. Nevertheless, at 16 h, the amount of cell debris in the limb\u2010buds was appreciable. Thin layer chromatography (TLC) of HU\u2010PG solution revealed no breakdown products or intermediate compounds suggesting that HU and PG do not react chemically. The presence of HU within both HU and HU\u2010PG treated embryos was confirmed by TLC of embryonic sonicants. In contrast, TLC of embryonic extracts revealed PG only in HU\u2010PG embryos. Light microscopy of other embryos from those same litters demonstrated extensive cell debris in the HU embryos but not in HU\u2010PG embryos. It is suggested that the delay in onset of HU cytotoxicity is caused by the antioxidant properties of PG acting within the embryos, and that this may account for the amelioration of HU teratogenesis by PG.<\/jats:p>","DOI":"10.1002\/tera.1420240104","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T14:40:12Z","timestamp":1118500812000},"page":"19-35","source":"Crossref","is-referenced-by-count":40,"title":["Amelioration of teratogenesis. I. Modification of hydroxyurea\u2010induced teratogenesis by the antioxidant propyl gallate"],"prefix":"10.1002","volume":"24","author":[{"given":"John M.","family":"DeSesso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,19]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"347","article-title":"Contractile response of isolated rabbit aortic strips to unsaturated fatty acid peroxides","volume":"208","author":"Asano M.","year":"1979","journal-title":"J. Pharmacol. Exp. 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