{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:56:23Z","timestamp":1791114983516,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,4,8]],"date-time":"2011-04-08T00:00:00Z","timestamp":1302220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Oxidative stress and reactive oxygen species (ROS) such as hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ), which is detoxified by catalase, are implicated in fetal death and birth defects. However, embryonic levels of catalase are only ~5% of adult activity, and its protective role is not understood completely. Herein, we used mutant catalasedeficient mice [acatalasemic (aCat)] and transgenic mice expressing human catalase (hCat), which, respectively, exhibited 40\u201050% reductions and 2\u2010fold elevations in the activities of embryonic and fetal brain catalase, to show that embryonic catalase protects the embryo from both physiological oxidative stress and the ROS\u2010initiating anti\u2010epileptic drug phenytoin. Compared to wild\u2010type (WT) catalase\u2010normal controls, both untreated and phenytoinexposed aCat mice exhibited a 30% increase in embryonic DNA oxidation and a &gt;2\u2010fold increase in embryopathies, both of which were completely blocked by protein therapy with exogenous catalase. Conversely, compared to WT controls, untreated and, to a lesser extent, phenytoinexposed hCat mice were protected, with untreated hCat embryos exhibiting a 40% decrease in embryonic DNA oxidation and up to a 67% decrease in embryopathies. Embryonic catalase accordingly plays an important protective role, and both physiological and phenytoin\u2010enhanced oxidative stress can be embryopathic.\u2014Abramov, J. P., Wells, P. G. Embryonic catalase protects against endogenous and phenytoin\u2010enhanced DNA oxidation and embryopathies in acatalasemic and human catalase\u2010expressing mice.\n                      <jats:italic>FASEB J.<\/jats:italic>\n                      25, 2188\u20102200 (2011).\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1096\/fj.11-182444","type":"journal-article","created":{"date-parts":[[2011,4,8]],"date-time":"2011-04-08T21:57:01Z","timestamp":1302299821000},"page":"2188-2200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Embryonic catalase protects against endogenous and phenytoin\u2010enhanced DNA oxidation and embryopathies in acatalasemic and human catalase\u2010expressing mice"],"prefix":"10.1096","volume":"25","author":[{"given":"Julia P.","family":"Abramov","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Wells","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Toronto Toronto Ontario Canada"},{"name":"Department of Pharmacology and Toxicology University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00201829"},{"key":"e_1_2_5_3_1","volume-title":"Free Radicals in Biology and Medicine","author":"Halliwell B.","year":"2007"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfn263"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.01.061"},{"key":"e_1_2_5_6_1","first-page":"264","article-title":"Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome\u2010encapsulated superoxide dismutase or catalase","volume":"132","author":"Padmanabhan R. V.","year":"1985","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_2_5_7_1","first-page":"H589","article-title":"Polyethylene glycol\u2010conjugated superoxide dismutase and catalase reduce ischemic brain injury","volume":"256","author":"Liu T. H.","year":"1989","journal-title":"Am. J. Physiol."},{"key":"e_1_2_5_8_1","first-page":"797","article-title":"Role of oxygen radicals and synergistic effect of superoxide dismutase and catalase on ischemia\u2010reperfusion injury of the rat pancreas","volume":"24","author":"Oda T.","year":"1992","journal-title":"Transplant. Proc."},{"key":"e_1_2_5_9_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3109\/10715769109145843","article-title":"Reduction of cold injury by superoxide dismutase and catalase","volume":"12","author":"Das D. K.","year":"1991","journal-title":"Free Rad. Res. Comm."},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1182\/blood.V88.3.1084.1084","article-title":"Active involvement of catalase during hemolytic crises of favism","volume":"88","author":"Gaetani G. F.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0026-895X(25)10035-7","article-title":"Phenytoin\u2010initiated DNA oxidation in murine embryo culture, and embryo protection by the antioxidative enzymes superoxide dismutase and catalase: evidence for reactive oxygen species\u2010mediated DNA oxidation in the molecular mechanism of phenytoin teratogenicity","volume":"48","author":"Winn L. M.","year":"1995","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_5_12_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF00405004","article-title":"Protection by free oxygen radical scavenging enzymes against glucose\u2010induced embryonic malformations in vitro","volume":"34","author":"Erickson U. J.","year":"1991","journal-title":"Diabetologia"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00193-2"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.1020110205"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr007"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051270303"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(95)00082-9"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5271com"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.11.1911"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-265X(73)90059-3"},{"key":"e_1_2_5_21_1","first-page":"384","article-title":"Ferrous ion oxidation in the presence of xylenol orange for the detection of lipid hydroperoxide in low density lipoprotein","volume":"202","author":"Jiang Z.\u2010Y.","year":"1992","journal-title":"Anal. Chem."},{"key":"e_1_2_5_22_1","first-page":"945","article-title":"A discontinuous method for catalase determination at \u201cnear physiological\u201d concentrations of H2O2 and its application to the study of H2O2 fluxes within cells","volume":"277","author":"Ou P.","year":"1996","journal-title":"J. Pharmacol. Exper. Ther."},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(85)80093-1"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.03.015"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2557-08.2008"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050259"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1996.tb00277.x"},{"key":"e_1_2_5_28_1","first-page":"2041","article-title":"High sensitivity to hepato\u2010tumorigenesis in hypocatalasemic C3H\/C(s) b\/Gen mice exposed to low doses of 252Cf fission neutrons and 60Co gamma\u2010rays","volume":"17","author":"Yamada K.","year":"1997","journal-title":"Anticancer Res."},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404800200"},{"key":"e_1_2_5_30_1","first-page":"5","article-title":"Free radical\u2010mediated mechanisms of anticonvulsant teratogenicity","volume":"2","author":"Wnn L. M.","year":"1995","journal-title":"Eur. J. Neurol."},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.1.111"},{"key":"e_1_2_5_32_1","doi-asserted-by":"crossref","first-page":"P204","DOI":"10.1016\/j.toxlet.2010.03.627","article-title":"Embryoprotective role of constitutive antioxidative catalase in wild\u2010type and acatalasemic mice in vivo and in embryo culture","volume":"196","author":"Perstin J. P.","year":"2010","journal-title":"Toxicol. Lett."},{"key":"e_1_2_5_33_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0026-895X(25)08685-7","article-title":"Phenytoin\u2010initiated hydroxyl radical formation: characterization by enhanced salicylate hydroxylation","volume":"49","author":"Kim P. M.","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.29116"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.100"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073808331082"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2005.05.002"},{"key":"e_1_2_5_38_1","first-page":"S71","article-title":"Low birthweight babies\u2013outcome at 13 years","volume":"46","author":"Nair M. K.","year":"2009","journal-title":"Indian Pediatr."},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2009.01.007"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10995-006-0158-z"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-005-0330-4"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199710)56:4<271::AID-TERA6>3.0.CO;2-1"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-197-43267"},{"key":"e_1_2_5_44_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0022-3565(25)21993-0","article-title":"Fetal anticonvulsant syndrome in rats: dose\u2010 and period\u2010response relationships of prenatal diphenylhydantoin, trimethadione and phenobarbital exposure on the structural and functional development of the offspring","volume":"227","author":"Vorhees C. V.","year":"1983","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420240202"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.94102145"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20177"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2946"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00323574"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00064-9"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.01901.x"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2006.01.007"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.12.016"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20090"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb01657.x"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1159\/000047185"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.2310\/6650.2001.33969"},{"key":"e_1_2_5_58_1","first-page":"418","article-title":"Protective role of low levels of constitutive catalase in embryonic and fetal development","volume":"79","author":"Perstin J.","year":"2007","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"e_1_2_5_59_1","first-page":"398","article-title":"Tissue drug concentrations, oxidative DNA damage and embryopathies in acatalasemic and catalase\u2010overexpressing embryos exposed in utero to phenytoin","volume":"85","author":"Perstin J.","year":"2009","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"e_1_2_5_60_1","first-page":"355","article-title":"Embryoprotective role of endogenous catalase in wild\u2010type (C3HeB\/FeJ) and acatalasemic (C3Ga.Cg\u2010Catb\/J) mice","volume":"108","author":"Perstin J.","year":"2009","journal-title":"Toxicol. Sci. (Suppl.: Toxicologist)"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-182444","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.11-182444","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-182444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:58:17Z","timestamp":1761674297000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.11-182444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4,8]]},"references-count":59,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1096\/fj.11-182444"],"URL":"https:\/\/doi.org\/10.1096\/fj.11-182444","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4,8]]},"assertion":[{"value":"2011-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-03-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}