| Valproic acid hepatotoxicity in human liver slices. | |
| | |
MedLine Citation:
|
PMID: 1811959 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Precision cut human liver slices were incubated in organ culture with valproic acid (VPA) to identify patterns of sensitivity to VPA-induced hepatotoxicity. The slices were incubated in Krebs-HEPES buffer supplemented with 25mM glucose and 84 micrograms/ml gentamycin. At 2, 4, 6, 12, 18 and 24 hr slices were taken and analyzed for K+ retention, synthesis of protein and LDH leakage. All three of these viability indicators showed that certain human livers were more susceptible to VPA-induced hepatotoxicity than others. In the limited group of human livers investigated (n = 9) we found one to be particularly sensitive and two relatively insensitive to VPA toxicity. The remaining tissues were of intermediate sensitivity towards VPA. At this time there is no correlation between the human livers that were susceptible to VPA induced hepatotoxicity and age or sex. This study was designed to show that VPA does induce hepatotoxicity in vitro at therapeutically relevant concentrations. Future studies will show whether VPA hepatotoxicity correlates with VPA metabolism, nutritional status or concomitant therapy. |
| | |
Authors:
|
R Fisher; H Nau; A J Gandolfi; C W Putnam; K Brendel |
Related Documents
:
|
2119269 - Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4... 9579899 - Successful treatment by direct hemoperfusion of coma possibly resulting from mitochondr... 3089669 - Valproate hydroxylation by human fetal tissues and embryotoxicity of metabolites. 20880119 - Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinica... 1432619 - Pharmacokinetic analysis of ester prodrugs of valproic acid. 22114689 - Boron stress activates the general amino acid control mechanism and inhibits protein sy... 572709 - Substrate specificity of a lipase preparation from geiotrichum asteroides as a function... 914659 - Phenidone-ascorbic acid development in electronmicroscopic autoradiography. 17135159 - Fatty acid composition of some medicinally useful seeds. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Drug and chemical toxicology Volume: 14 ISSN: 0148-0545 ISO Abbreviation: Drug Chem Toxicol Publication Date: 1991 |
Date Detail:
|
Created Date: 1992-06-10 Completed Date: 1992-06-10 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 7801723 Medline TA: Drug Chem Toxicol Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 375-94 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, University of Arizona, Tucson. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Aged Child Child, Preschool Culture Techniques Dose-Response Relationship, Drug Female Humans L-Lactate Dehydrogenase / metabolism Liver / chemistry, drug effects*, metabolism Male Middle Aged Potassium / analysis Valproic Acid / toxicity* |
| Grant Support | |
ID/Acronym/Agency:
|
GM 38290/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
7440-09-7/Potassium; 99-66-1/Valproic Acid; EC 1.1.1.27/L-Lactate Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Toxicity and mutagenicity of the molluscicidal plant Ambrosia maritima L.
Next Document: Toxicological study of pyridoxal isonicotinoyl hydrazone: acute and subchronic toxicity.