Literature DB >> 6414476

Action of the antiepileptic drug, valproic acid, on fatty acid oxidation in isolated rat hepatocytes.

F X Coudé, G Grimber, A Pelet, Y Benoit.   

Abstract

Valproate at 0.1 to 5 mM strongly inhibited oxidation of 1-(14C)-palmitate in isolated rat hepatocytes. Valproate at the same concentrations markedly decreased ketogenesis from 1 mM oleate. Valproate in a dose up to 5 mM did not significantly affect cellular concentration of ATP but lowered beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios which paralleled its effect on ketogenesis. Moreover concomitant acetyl-CoA levels were drastically decreased by valproate. From this it may be concluded that inhibition of fatty acid oxidation by valproate results in reduced production of two carbons units and a drop of NADH/NAD+ ratio in rat hepatocyte. This suggests that valproate seriously interferes with beta-oxidation of physiological long-chain fatty acids.

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Year:  1983        PMID： 6414476     DOI： 10.1016/s0006-291x(83)80205-8

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN： 0006-291X            Impact factor:   3.575


  10 in total

Review 1.  Valproate-induced Fanconi syndrome in a 27-year-old woman.

Authors:  Sandeep M Patel; Jonathan Graff-Radford; Mark L Wieland
Journal:  J Gen Intern Med       Date:  2011-04-23       Impact factor: 5.128

Review 2.  Biochemical relationships between Reye's and Reye's-like metabolic and toxicological syndromes.

Authors:  J Osterloh; W Cunningham; A Dixon; D Combest
Journal:  Med Toxicol Adverse Drug Exp       Date:  1989 Jul-Aug

3.  Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.

Authors:  Li-fang Zhang; Ling-sheng Liu; Xiao-man Chu; Hao Xie; Li-juan Cao; Cen Guo; Ji-ye A; Bei Cao; Meng-jie Li; Guang-ji Wang; Hai-ping Hao
Journal:  Acta Pharmacol Sin       Date:  2014-01-20       Impact factor: 6.150

4.  Acetate represents a major product of heptanoate and octanoate beta-oxidation in hepatocytes isolated from neonatal piglets.

Authors:  X Lin; S H Adams; J Odle
Journal:  Biochem J       Date:  1996-08-15       Impact factor: 3.857

5.  Complete beta-oxidation of valproate: cleavage of 3-oxovalproyl-CoA by a mitochondrial 3-oxoacyl-CoA thiolase.

Authors:  Margarida F B Silva; Jos P N Ruiter; Henk Overmars; Albert H Bootsma; Albert H van Gennip; Cornelis Jakobs; Marinus Duran; Isabel Tavares de Almeida; Ronald J A Wanders
Journal:  Biochem J       Date:  2002-03-15       Impact factor: 3.857

6.  A Histone Deacetylase Inhibitor Induces Acetyl-CoA Depletion Leading to Lethal Metabolic Stress in RAS-Pathway Activated Cells.

Authors:  Agnes Basseville; Pierre-Christian Violet; Maryam Safari; Carole Sourbier; W Marston Linehan; Robert W Robey; Mark Levine; Dan L Sackett; Susan E Bates
Journal:  Cancers (Basel)       Date:  2022-05-26       Impact factor: 6.575

Review 7.  Valproate-associated hepatotoxicity and its biochemical mechanisms.

Authors:  M J Eadie; W D Hooper; R G Dickinson
Journal:  Med Toxicol Adverse Drug Exp       Date:  1988 Mar-Apr

8.  Glucose metabolism as a target of histone deacetylase inhibitors.

Authors:  Suzanne E Wardell; Olga R Ilkayeva; Heather L Wieman; Daniel E Frigo; Jeffrey C Rathmell; Christopher B Newgard; Donald P McDonnell
Journal:  Mol Endocrinol       Date:  2008-12-23

Review 9.  Valproate hepatotoxicity syndrome: hypotheses of pathogenesis.

Authors:  J R Stephens; R H Levy
Journal:  Pharm Weekbl Sci       Date:  1992-06-19

10.  Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms.

Authors:  M E Coakley; S J Rawlings; N A Brown
Journal:  Environ Health Perspect       Date:  1986-12       Impact factor: 9.031
  10 in total

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