NDLI: The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid.

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The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid.

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The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lee, Min Sun Lee, Young-Joo Kim, Bo Joon Shin, Kye Jung Chung, Bong Chul Baek, Du-Jong Jung, Byung Hwa
Description	Author Affiliation: Lee MS ( Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, Seoul, 136-791, Korea.)
Abstract	The aim of this study was to investigate the relationship between hepatotoxicity, levels of glucuronide conjugates of valproic acid (VPA), and the toxic metabolites of VPA (4-ene VPA and 2,4-diene VPA). We also examined whether hepatotoxicity could be predicted by the urinary excretion levels of VPA and its toxic metabolites. VPA was administrated orally in rats in amounts ranging from 20 mg/kg to 500 mg/kg. Free and total (free plus glucuronide conjugated) VPA, 4-ene VPA, and 2,4-diene VPA were quantified in urine and liver using gas chromatography-mass spectrometry. Serum levels of aspartate aminotransferase, alanine aminotransferase, and alpha-glutathione S-transferase (alpha-GST) were also determined to measure the level of hepatotoxicity. The serum alpha-GST level increased slightly at the 20 mg/kg dose, and substantially increased at the 100 and 500 mg/kg dose; aspartate aminotransferase and alanine aminotransferase levels did not change with the administration of increasing doses of VPA. The liver concentration of free 4-ene VPA and the urinary excretion of total 4-ene VPA were the only measures that correlated with the increase in the serum alpha-GST level (p < 0.094 and p < 0.023 respectively). From these results, we conclude that hepatotoxicity of VPA correlates with liver concentration of 4-ene VPA and can be predicted by the urinary excretion of total 4-ene VPA.
File Format	HTM / HTML
ISSN	02536269
Issue Number	7
Volume Number	32
e-ISSN	19763786
Journal	Archives of Pharmacal Research
Language	English
Publisher	Springer
Publisher Date	2009-07-01
Publisher Place	Korea (South)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Anticonvulsants Pharmacokinetics Toxicity Drug-induced Liver Injury Liver Drug Effects Valproic Acid Administration, Oral Alanine Transaminase Blood Animals Administration & Dosage Urine Aspartate Aminotransferases Biotransformation Dose-response Relationship, Drug Fatty Acids, Monounsaturated Gas Chromatography-mass Spectrometry Glutathione Transferase Isoenzymes Metabolism Liver Diseases Male Rats Rats, Sprague-dawley Analogs & Derivatives Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Drug Discovery Molecular Medicine

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