Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca.
- D. Mckenna, G. Towers, F. Abbott
- BiologyJournal of Ethnopharmacology
- 1 April 1984
Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats.
- V. Tong, X. Teng, Thomas K. H. Chang, F. Abbott
- BiologyToxicological Sciences
- 1 August 2005
Overall, these findings indicate that VPA treatment results in oxidative stress, as measured by levels of 15-F(2t)-IsoP, which precedes the onset of necrosis, steatosis, and elevated levels of serum alpha-GST.
Valproic acid II: effects on oxidative stress, mitochondrial membrane potential, and cytotoxicity in glutathione-depleted rat hepatocytes.
- V. Tong, X. Teng, Thomas K. H. Chang, F. Abbott
- Biology, MedicineToxicological Sciences
- 1 August 2005
It is indicated that acute treatment of freshly isolated rat hepatocytes with VPA resulted in oxidative stress, which occurred in the absence of cytotoxicity, and that glutathione confers protection to hepatocytes against mitochondrial damage by VPA.
Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes
Overall, the homozygote and heterozygote CYP2C9*2 and CYP9*3 genotypes may compromise hepatic VPA biotransformation.
Contribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype.
- Tony K. L. Kiang, P. Ho, M. Anari, V. Tong, F. Abbott, Thomas K. H. Chang
- Biology, ChemistryToxicological Sciences
- 1 December 2006
Overall, the novel findings indicate that in human hepatic microsomes, CYP2C9*1 is the predominant catalyst in the formation of 4-ene-VPA, 4-OH- VPA, and 5- OH-Vpa, whereas CyP2A6 contributes partially to 3-OH -VPA formation.
Oxidative Stress as a Mechanism of Valproic Acid-Associated Hepatotoxicity
- Thomas K. H. Chang, F. Abbott
- BiologyDrug metabolism reviews (Softcover ed.)
- 1 January 2006
Experimental evidence on the effect of VPA on the various indices of oxidative stress and on the potential role of oxidative Stress in VPA-associated hepatotoxicity are discussed.
In vivo formation of the thiol conjugates of reactive metabolites of 4-ene VPA and its analog 4-pentenoic acid.
- K. Kassahun, F. Abbott
- Chemistry, BiologyDrug Metabolism And Disposition
- 1 November 1993
Isolation of the thiol conjugates of 3-oxo-4-pentenoic acid provides the first direct spectroscopic evidence for the in vivo formation of the metabolite of 4-pentenosic acid considered responsible for the irreversible inhibition of fatty acid metabolism.
Fluorinated analogues as mechanistic probes in valproic acid hepatotoxicity: hepatic microvesicular steatosis and glutathione status.
- W. Tang, A. Borel, T. Fujimiya, F. Abbott
- Biology, ChemistryChemical Research in Toxicology
- 1 July 1995
The theory that hepatotoxicant 4-ene VPA, and possibly VPA itself, is mediated largely through beta-oxidation of 4-enes VPA to reactive intermediates that are capable of depleting mitochondrial GSH is supported.
Effects of Age and Polytherapy, Risk Factors of Valproic Acid (VPA) Hepatotoxicity, on the Excretion of Thiol Conjugates of (E)‐2,4‐diene VPA in People with Epilepsy Taking VPA
- S. Gopaul, K. Farrell, F. Abbott
- Medicine, BiologyEpilepsia
- 1 March 2003
It is demonstrated here that the thiol conjugates of (E)‐2,4‐diene VPA were significantly elevated in a high‐risk group of patients.
Chemistry and biotransformation
The current chapter describes the chemistry and structure-activity relationships (SAR) of VPA analogues and related metabolites, followed by an overview on the metabolic pathways involved in VPA biotransformation.
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