{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:02:27Z","timestamp":1778569347613,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T00:00:00Z","timestamp":1192492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sodium dehydroacetate (DHA\u2010S) is used as a food additive, preservative and antimicrobial agent. Repeated oral administration of DHA\u2010S in rats induced severe hemorrhage in multiple organs and prolongation of blood coagulation factors. To determine the mechanism of hemorrhage, the protective effect of vitamin K (VK) was investigated. Increased VK\u2010dependent blood coagulation parameters, a prolonged prothrombin time (PT) and an activated partial thromboplastin time (APTT) were observed in rats when DHA\u2010S alone was administered, while only a slight change was observed in animals that received a single injection of vitamin K<jats:sub>2<\/jats:sub> following the DHA\u2010S dosing. These results suggest that DHA\u2010S\u2010induced hemorrhage is caused by a deficiency of vitamin K. In addition, the inhibitory effect of DHA\u2010S on vitamin K<jats:sub>1<\/jats:sub> epoxide reductase (VKOR) activity was measured with an <jats:italic>in vitro<\/jats:italic> system using liver microsomes of normal male rats. DHA\u2010S concentration\u2010dependently inhibited VKOR activity similar to warfarin, but the inhibitory concentration was high. Therefore, it was concluded that the DHA\u2010S\u2010induced hemorrhage was caused by a depletion of blood VK, associated with any factors including VKOR inhibition. Copyright \u00a9 2007 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1304","type":"journal-article","created":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T13:16:40Z","timestamp":1192540600000},"page":"524-529","source":"Crossref","is-referenced-by-count":23,"title":["Anticoagulant effect of sodium dehydroacetate (DHA\u2010S) in rats"],"prefix":"10.1002","volume":"28","author":[{"given":"Yuka","family":"Sakaguchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Suga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiyu","family":"Oshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Miyamoto\u2010Kuramitsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,10,16]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"290","article-title":"Untersuchungen uber die umwandlung von verfutterten K\u2010vitaminen durch austausch der seitenkette und die rolle der darmbakterien hierbei","volume":"340","author":"Billeter M","year":"1964","journal-title":"Biochem. Z."},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1055\/s-0037-1615151","article-title":"Warfarin resistance is associated with a protein component of the vitamin K 2,3\u2010epoxide reductase enzyme complex in rat liver","volume":"80","author":"Cain D","year":"1998","journal-title":"Thromb. Haemost."},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1995.tb05819.x"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/10915818509078671"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2001.28590"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.3358\/shokueishi.42.404"},{"key":"e_1_2_1_8_1","first-page":"27","article-title":"Morphological studies on the liver of mice administered with dehydroacetic acid","volume":"8","author":"Kanai K","year":"1981","journal-title":"Kankyo Kagaku Sogo Kenkyujo Nenpo"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.29.13"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8588(18)30273-9"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0022-3565(25)11412-2","article-title":"The relationship between the vitamin K cycle inhibition and the plasma anticoagulant response at steady\u2010state S\u2010warfarin conditions in the rat","volume":"260","author":"Mosterd JJ","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(85)90291-0"},{"key":"e_1_2_1_13_1","first-page":"405","article-title":"The pathogenesis of decreased aspartate aminotransferase and alanine aminotransferase activity in the plasma of hemodialysis patients: the role of vitamin B6 deficiency","volume":"43","author":"Ono K","year":"1995","journal-title":"Clin. Nephrol."},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(88)90750-2"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0308-2261(21)00482-3","article-title":"Acquired coagulation disorders","volume":"14","author":"Prentice CR","year":"1985","journal-title":"Clin. Haematol."},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.19803130411"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(88)90346-2"},{"key":"e_1_2_1_18_1","first-page":"322","article-title":"Changes of phylloquinone and menaquinone\u20104 concentrations in rat liver after oral, intravenous and intraperitoneal administration","volume":"66","author":"Sakamoto N","year":"1996","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"e_1_2_1_19_1","first-page":"69","article-title":"Dehydroacetic acid (DHA). II. General pharmacology and mechanism of action","volume":"99","author":"Seevers MH","year":"1950","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1990.00156.x"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0022-3565(25)04227-2","article-title":"Dehydroacetic acid (DHA). I. Acute and chronic toxicity","volume":"99","author":"Spencer HC","year":"1950","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1515\/DMDI.1987.5.4.225"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.67.406"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1254\/fpj.67.419"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90260-7"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01867a066"},{"key":"e_1_2_1_27_1","first-page":"166","article-title":"Studies on the acute oral toxicity of dehydroacetic acid, sorbic acid and their combination compound in rats","volume":"103","author":"Uchida O","year":"1985","journal-title":"Eisei Shikenjo Hokoku"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.1304","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.1304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:27:11Z","timestamp":1760542031000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.1304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10,16]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2008,5]]}},"alternative-id":["10.1002\/jat.1304"],"URL":"https:\/\/doi.org\/10.1002\/jat.1304","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10,16]]}}}