{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:25:16Z","timestamp":1760549116599,"version":"3.30.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":11992,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1982,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The administration of high\u2013dose valproic acid (VPA) (750 mg per kg) consistently produced significant microvesicular steatosis in mature Sprague\u2013Dawley rats after 48 hr. Similar changes occurred in animals pretreated with phenobarbital which received a lower dose of VPA (350 mg per kg), but no steatosis was seen in animals treated with the low\u2013dose VPA alone. The steatogenic effect of VPA is most likely mediated by a toxic metabolite. It can also be speculated that phenobarbital, by enhancing the inducing effects of the hepatic mixed\u2013function oxidase system, may lead to increased conversion of VPA to a toxic metabolite. Young and weanling rats appeared to be resistant to the steatogenic effects of VPA. Reproduction of microvesicular steatosis in this experimental model may permit exploration of factors that enhance or inhibit VPA\u2013induced hepatic injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840020622","type":"journal-article","created":{"date-parts":[[2011,7,15]],"date-time":"2011-07-15T10:16:04Z","timestamp":1310724964000},"page":"870-873","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":77,"title":["Valproate\u2013Induced Hepatic Steatogenesis in Rats"],"prefix":"10.1097","volume":"2","author":[{"given":"James H.","family":"Lewis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyman J.","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlton T.","family":"Garrett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliot","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840020622-BIB1|cit1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1056\/NEJM198003203021204","article-title":"Valproic acid","volume":"302","author":"Brown","year":"1980","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840020622-BIB2|cit2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1056\/NEJM197908233010817","article-title":"Hepatic failure from valproic acid (letter)","volume":"301","author":"Bowdle","year":"1979","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840020622-BIB3|cit3","first-page":"273","article-title":"Valproic acid and fatal hepatitis","volume":"29","author":"Donat","year":"1979","journal-title":"Neurology"},{"key":"10.1002\/hep.1840020622-BIB4|cit4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0022-3476(79)80110-9","article-title":"Reye-like syndrome associated with valproic acid therapy","volume":"95","author":"Gerber","year":"1979","journal-title":"J Pediatr"},{"key":"10.1002\/hep.1840020622-BIB5|cit5","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1056\/NEJM197904263001706","article-title":"Acute hepatic failure associated with the use of sodium valproate: report of two fatal cases","volume":"300","author":"Suchy","year":"1979","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840020622-BIB6|cit6","first-page":"110","article-title":"Acute liver disease associated with sodium valproate (letter)","volume":"2","author":"Ware","year":"1980","journal-title":"Lancet"},{"key":"10.1002\/hep.1840020622-BIB7|cit7","first-page":"436","article-title":"Hepatic failure from valproic acid (letter)","volume":"301","author":"Mathis","year":"1979","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840020622-BIB8|cit8","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S0140-6736(80)92861-5","article-title":"Fatal hepatotoxicity in child on phenobarbitone and sodium valproate","volume":"1","author":"Jacobi","year":"1980","journal-title":"Lancet"},{"key":"10.1002\/hep.1840020622-BIB9|cit9","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/S0140-6736(80)92359-4","article-title":"Fatal hepatic failure and sodium valproate","volume":"2","author":"LeBihan","year":"1980","journal-title":"Lancet"},{"key":"10.1002\/hep.1840020622-BIB10|cit10","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0016-5085(19)32471-0","article-title":"The hepatic lesion in Reye's syndrome","volume":"69","author":"Bove","year":"1975","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840020622-BIB11|cit11","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1056\/NEJM197608262950901","article-title":"Jamaican vomiting sickness: biochemical investigation of two cases","volume":"295","author":"Tanaka","year":"1976","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840020622-BIB12|cit12","first-page":"111","volume-title":"Antiepileptic therapy: advances in drug monitoring","author":"Kochen","year":"1980"},{"key":"10.1002\/hep.1840020622-BIB13|cit13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1203\/00006450-197503000-00005","article-title":"Production of the features of Reye's syndrome in rats with 4-pentenoic acid","volume":"9","author":"Glasgow","year":"1975","journal-title":"Pediatr Res"},{"key":"10.1002\/hep.1840020622-BIB14|cit14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1528-1157.1977.tb04465.x","article-title":"Metabolism of valproate sodium in rabbit, rat, dog and man","volume":"18","author":"Ferrandes","year":"1977","journal-title":"Epilepsia"},{"key":"10.1002\/hep.1840020622-BIB15|cit15","first-page":"59","volume-title":"Hepatotoxicity; 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