{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:24:19Z","timestamp":1791257059925,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,6,5]],"date-time":"2005-06-05T00:00:00Z","timestamp":1117929600000},"content-version":"vor","delay-in-days":4114,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1994,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To test the hypothesis that cocaine\u2010induced embryonic vascular disruption is mediated by oxygen free radicals, the antioxidants 2\u2010oxothiazolodine\u20104\u2010carboxylate (OTC) and \u03b1\u2010phenyl\u2010N\u2010<jats:italic>t<\/jats:italic>\u2010butylnitrone (PBN) were employed. When cocaine (78 mg\/kg) was administered on day 8 of gestation to ICR mice and embryos evaluated on day 10 (in vivo), 62.3% of cocainetreated embryos showed increased vasodilation compared to 4.9% for controls, and 33.1% of the cocaine\u2010exposed embryos showed marked hemorrhage compared to 3.3% for controls. In addition, cocaine increased the incidence of neural defects, in the form of open neural tube, hypoplastic prosencephalon, and microcephaly. Administration of OTC (0.25 and 0.5 mmol\/kg) or PBN (300 mg\/kg) prior to cocaine significantly reduced cocaine\u2010induced vasodilation and hemorrhage, while not preventing neural defects. When cocaine (78 mg\/kg) was administered in vivo on day 8 of gestation and embryos were dissected 15 min later and subsequently cultured for 48 hr in the absence of cocaine (in vivo\u2010in vitro), marked vascular disruption was observed: normal yolk circulation\/heartbeat was decreased to 26.6%, while edema\/blisters and vasodilation\/hemorrhorage were increased to 45.6% and 59.6%, respectively. Administration of PBN (300 mg\/kg) prior to cocaine completely prevented cocaine\u2010induced vascular disruption. When cocaine was administered in vivo and PBN (300 \u03bcg\/ml) was incubated with cultured embryos in vitro, the antioxidant only partially prevented cocaine\u2010induced cardiovascular defects in this model. Neural defects produced by cocaine were not significantly affected by PBN, administered either in vivo or in vitro. Cocaine (78 mg\/kg) administered in vivo stimulated lipid peroxidation maximally after 3 hr in both day 8 and day 9 embryos. When cocaine was incubated in vitro during embryo culture at 33 \u03bcg\/ml), a concentration that produces nonspecific inhibition of growth and development, embryonic lipid peroxidation on day 9 was not affected. Finally, when PBN (300 mg\/kg) was administered prior to cocaine (78 mg\/kg) on day 8 of gestation, stimulation of lipid peroxidation by cocaine was prevented. These results suggest that cocaine\u2010induced vascular disruption in early development is mediated by maternal production of oxygen free radicals. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/tera.1420490315","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:01:41Z","timestamp":1118505701000},"page":"192-201","source":"Crossref","is-referenced-by-count":52,"title":["Role of oxygen free radicals in cocaine\u2010induced vascular disruption in mice"],"prefix":"10.1002","volume":"49","author":[{"given":"Ernest F.","family":"Zimmerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju B.","family":"Potturi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Resnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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