Linked Life Data

1493781

Source:http://linkedlifedata.com/resource/pubmed/id/1493781

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-3-8
pubmed:abstractText
E-2-en-Valproate (E-2-en-VPA; trans-2-en-VPA) and VPA were studied for potential hepatotoxicity in young male Sprague-Dawley rats. Both drugs were administered daily at 750 mg/kg i.p. (divided into three doses a day) for 7 consecutive days. Clinical chemistry parameters were studied before and after the period of treatment. Furthermore, the drug pharmacokinetics and metabolism were analyzed at onset and end of the prolonged administration. Treatment with VPA induced hyperammonemia and other alterations in liver function tests which were not observed after treatment with E-2-en-VPA, although plasma levels of both drugs were comparable. The pharmacokinetics of VPA and E-2-en-VPA in young rats were similar, but analysis of metabolites by gas chromatography-mass spectrometry indicated marked differences in the metabolite profile, e.g., a lack of the suspected hepatotoxic metabolite 4-en-VPA in plasma of rats treated with E-2-en-VPA. Histopathological examination of liver sections showed that VPA and E-2-en-VPA did not induce degenerative liver lesions or significant alterations in hepatic content and distribution of lipids and glycogen at the doses administered. Only one of the VPA treated rats showed fatty infiltration (microvesicular steatosis). The data demonstrate that, although E-2-en-VPA is more potent than VPA as an anticonvulsant in rats, it does not exert more potent hepatotoxic effects and does not alter ammonia metabolism. Thus the data substantiate previous experimental studies that E-2-en-VPA might be a valuable substitute for VPA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0920-1211
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
187-98
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Effects of valproate and E-2-en-valproate on functional and morphological parameters of rat liver. I. Biochemical, histopathological and pharmacokinetic studies.
pubmed:affiliation
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
pubmed:publicationType
Journal Article