Molecular and Therapeutic Potential and Toxicity of Valproic Acid

Chateauvieux, Sébastien; Morceau, Franck; Dicato, Mario; Diederich, Marc

doi:10.1155/2010/479364

Cited by 380 publications

(321 citation statements)

References 138 publications

(139 reference statements)

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“…The dual inhibition of HDAC and GSK3β by VPA may provide a basis for its anticancer activity. As expected, clinical trials using VPA for cancer showed some effects (Chateauvieux et al, 2010). Significant inhibitory effects for GSK3β are clearly observed at VPA concentrations approximating those attained clinically during treatment.…”

Section: Valproic Acid (Vpa)supporting

confidence: 78%

The Pivotal Roles of GSK3β in Glioma Biology

Nakada¹,

Minamoto²,

Pyko³

et al. 2011

Molecular Targets of CNS Tumors

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Section: Valproic Acid (Vpa)supporting

confidence: 78%

The Pivotal Roles of GSK3β in Glioma Biology

Nakada¹,

Minamoto²,

Pyko³

et al. 2011

Molecular Targets of CNS Tumors

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“…Moreover, VPA inhibits T-type calcium channels, voltage-dependent sodium channels, 45 and also signaling pathways of TNF-␣, NF-B, and IL-6. 22,46 It would also be worthwhile to investigate the effect of VPA on the renal progenitor cell population. Thus far, TSA and 4-phenylthiobutanoic acid were shown to expand the renal progenitor cell population.…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Attenuates Proteinuria and Kidney Injury

Beneden

Geers

Pauwels

et al. 2011

Journal of the American Society of Nephrology

112

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Inhibitors of histone deacetylase (HDAC) have anti-inflammatory and antifibrotic effects in several organs and tissues, but their effect on the progression of renal disease is unknown. Here, we studied the effect of valproic acid in adriamycin-induced nephropathy in mice. Administration of valproic acid before kidney injury prevented the development of proteinuria and the onset of glomerulosclerosis. Even after postponing treatment until the peak of adriamycin-induced proteinuria, valproic acid rapidly decreased the quantity of proteinuria and attenuated the progression of renal disease. Valproic acid abrogated the decrease in glomerular acetylation observed during adriamycin-induced nephropathy. Furthermore, valproic acid attenuated the significant upregulation of profibrotic and proinflammatory genes, the deposition of collagen, and the infiltration of macrophages into the kidney. Valproic acid decreased glomerular apoptosis and proliferation induced by adriamycin. Ultrastructural studies further supported the protective effect of valproic acid on podocytes in this model. Taken together, these data suggest that HDACs contribute to the pathogenesis of renal disease and that HDAC inhibitors may have therapeutic potential in CKD.

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“…In recent years, pharmaceutical companies have developed new AEDs with improved safety profiles than the previously available ones. Several studies have described the toxicity of AEDs to neuronal cells, in vitro and in vivo, Chateauvieux et al, 2010;Landmark and Johannessen, 2008;Manent et al, 2008), but the mechanisms underlying the toxic effects of AEDs in neuronal cells are still a matter of debate.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

Morte

Carreira

Falcão

et al. 2013

Toxicology in Vitro

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a b s t r a c tIn this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellularregulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK).We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3 mM, for 24 h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/ JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK.These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent.

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Molecular and Therapeutic Potential and Toxicity of Valproic Acid

Cited by 380 publications

References 138 publications

The Pivotal Roles of GSK3β in Glioma Biology

The Pivotal Roles of GSK3β in Glioma Biology

Valproic Acid Attenuates Proteinuria and Kidney Injury

Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

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