{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:32:03Z","timestamp":1790775123652,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2007,7,11]],"date-time":"2007-07-11T00:00:00Z","timestamp":1184112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Diabetic teratogenicity relates, partly, to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We investigated the effects of superoxide dismutase\u2010mimics nitroxides, 2,2,6,6\u2010tetramethyl piperidine\u2010N\u2010oxyl (TPL) as an effective antioxidant, on diabetes\u2010induced embryopathy. <jats:bold>METHODS:<\/jats:bold> Embryos (10.5 day old) and their yolk sacs from Sabra female rats were cultured for 28 h in the absence or in the presence of nitroxides at 0.05\u20130.4 m<jats:italic>M<\/jats:italic> in control, diabetic subteratogenic, or diabetic teratogenic media, and monitored for growth retardation and congenital anomalies. The oxidant\/antioxidant status was examined by oxygen radical absorbance capacity and lipid peroxidation assays, whereas the yolk sac function was evaluated by endocytosis assay. <jats:bold>RESULTS:<\/jats:bold> Diabetic culture medium inhibited embryonic and yolk sac growth, induced a high rate of NTDs, reduced yolk sac endocytosis and embryonic antioxidant capacity, and increased lipid peroxidation. These effects were more prominent in the embryos with NTD compared to those without NTD. TPL added to diabetic teratogenic medium improved embryonic and yolk sac growth, reduced the rate of NTDs, and improved yolk sac function. The oxidant\/antioxidant status of embryos was also improved. TPL at 1 m<jats:italic>M<\/jats:italic> did not damage the embryos cultured in control medium. <jats:bold>CONCLUSIONS:<\/jats:bold> In diabetic culture medium, oxidative damage is higher in the malformed rat embryos compared to those without anomalies; the nitroxide provides protection againstdiabetes\u2010induced teratogenicity in a dose\u2010dependent manner. The yolk sac damage, apparently caused by the same mechanism, might be an additional contributor to the embryonic damage observed in diabetes. Birth Defects Research (Part A), 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20383","type":"journal-article","created":{"date-parts":[[2007,7,11]],"date-time":"2007-07-11T19:43:16Z","timestamp":1184182996000},"page":"604-611","source":"Crossref","is-referenced-by-count":19,"title":["Nitroxide radicals protect cultured rat embryos and yolk sacs from diabetic\u2010induced damage"],"prefix":"10.1002","volume":"79","author":[{"given":"Seonghun","family":"Ryu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni","family":"Kohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amram","family":"Samuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher","family":"Ornoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,8,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420440206"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420240108"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.1.101"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00405004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/03009734000000055"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6215(00)00129-4"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0113732"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.09.037"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6215(00)00059-8"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420410403"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.37.3.386"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408449309104073"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420340313"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(03)00270-3"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90342-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(91)90442-L"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.1978.tb00993.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199912)60:6<376::AID-TERA10>3.0.CO;2-Q"},{"key":"e_1_2_6_21_1","first-page":"43","article-title":"Effects of sera from Cohen, genetically determined diabetic rats, streptozotocin diabetic rats and sucrose fed rats on in vitro development of early somite rat embryos","volume":"3","author":"Ornoy A","year":"1986","journal-title":"Diabetes Res"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(86)80001-1"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420330110"},{"key":"e_1_2_6_24_1","first-page":"755","article-title":"Yolk sac failure in embryopathy due to hyperglycemia: horseradish peroxidase uptake in the assessment of yolk sac function","volume":"74","author":"Reece EA","year":"1989","journal-title":"Obstet Gynecol"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"17921","DOI":"10.1016\/S0021-9258(19)81304-2","article-title":"A novel metal\u2010free low molecular weight superoxide dismutase mimic","volume":"263","author":"Samuni A","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10043"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.4.813"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1034"},{"key":"e_1_2_6_29_1","first-page":"112","article-title":"Quantitative studies of pinocytosis. 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