1,690 results match your criteria Toxicity Valproate


A sub-chronic Xysmalobium undulatum hepatotoxicity investigation in HepG2/C3A spheroid cultures compared to an in vivo model.

J Ethnopharmacol 2019 Apr 19:111897. Epub 2019 Apr 19.

Pharmacen™, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230, Odense M, Denmark; Celvivo IVS, Blommenslyst, Denmark. Electronic address:

Ethnopharmacology Relevance: Traditional herbal medicines are utilized by 27 million South Africans. Xysmalobium undulatum (Uzara) is one of the most widely used traditional medicinal plants in Southern Africa. A false belief in the safety of herbal medicine may result in liver injury. Read More

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http://dx.doi.org/10.1016/j.jep.2019.111897DOI Listing

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 May 28;4(1):75-100. Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410631PMC
May 2018
3 Reads

Adverse drug reactions of anti-epileptic drugs in children with epilepsy: a cross-sectional study Running Title: Adverse drug reactions to Anti-epileptic drugs.

Curr Drug Saf 2019 Mar 10. Epub 2019 Mar 10.

Department of Pediatrics, School of Medical Sciences &Research, Sharda University, Greater Noida, Uttar Pradesh 201310. India.

Background: Adverse drug reactions (ADRs) due to antiepileptic drugs (AEDs) in children contribute to poorer patient outcomes. However, we lack reliable data on the burden of such ADRs.

Objectives: Thus, the aim of the present study was to determine the incidence and patterns of ADRs of antiepileptic drugs in children aged 2-17 years presenting to a tertiary care teaching hospital. Read More

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http://dx.doi.org/10.2174/1574886314666190311112710DOI Listing
March 2019
1 Read

Topiramate for juvenile myoclonic epilepsy.

Cochrane Database Syst Rev 2019 01 28;1:CD010008. Epub 2019 Jan 28.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Beijing, China, 100053.

Background: Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. Read More

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http://doi.wiley.com/10.1002/14651858.CD010008.pub4
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http://dx.doi.org/10.1002/14651858.CD010008.pub4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353083PMC
January 2019
6 Reads

Differential Hepatotoxic Effects of Sodium Valproate at Different Doses in Albino Rats.

Kathmandu Univ Med J (KUMJ) 2018 Jan.-Mar;16(61):78-82

Department of Anatomy, Kathmandu University School of Medical Sciences, Dhulikhel, Kavre, Nepal.

Background Liver plays an essential role for transforming and clearing chemicals that may cause harmful effects to it. Sodium Valproate, renowned to be a potent antiepileptic drug, when taken in overdose may cause toxic effects to liver and other organs as well. Liver damage can be assessed with histological changes and measurement of enzymes produced by it. Read More

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February 2019
3 Reads

Comparative efficacy of valnoctamide and sec-butylpropylacetamide (SPD) in terminating nerve agent-induced seizures in pediatric rats.

Epilepsia 2019 Feb 7;60(2):315-321. Epub 2019 Jan 7.

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

Objectives: Children and adults are likely to be among the casualties in a civilian nerve agent exposure. This study evaluated the efficacy of valnoctamide (racemic-VCD), sec-butylpropylacetamide (racemic-SPD), and phenobarbital for stopping nerve agent seizures in both immature and adult rats.

Methods: Female and male postnatal day (PND) 21, 28, and 70 (adult) rats, previously implanted with electroencephalography (EEG) electrodes were exposed to seizure-inducing doses of the nerve agents sarin or VX and EEG was recorded continuously. Read More

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http://dx.doi.org/10.1111/epi.14630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419725PMC
February 2019
4 Reads

Neuroglia in the autistic brain: evidence from a preclinical model.

Mol Autism 2018 27;9:66. Epub 2018 Dec 27.

1Department of Physiology and Pharmacology, "Vittorio Erspamer" SAPIENZA University of Rome, 00185 Rome, Italy.

Background: Neuroglial cells that provide homeostatic support and form defence of the nervous system contribute to all neurological disorders. We analyzed three major types of neuroglia, astrocytes, oligodendrocytes, and microglia in the brains of an animal model of autism spectrum disorder, in which rats were exposed prenatally to antiepileptic and mood stabilizer drug valproic acid; this model being of acknowledged clinical relevance.

Methods: We tested the autistic-like behaviors of valproic acid-prenatally exposed male rats by performing isolation-induced ultrasonic vocalizations, the three-chamber test, and the hole board test. Read More

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http://dx.doi.org/10.1186/s13229-018-0254-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307226PMC
January 2019
2 Reads

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications.

Environ Toxicol Pharmacol 2019 Feb 19;66:14-23. Epub 2018 Dec 19.

College of Public Health, Zhengzhou University, Zhengzhou, PR China. Electronic address:

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Read More

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http://dx.doi.org/10.1016/j.etap.2018.12.015DOI Listing
February 2019
5 Reads

The Combination of Metformin and Valproic Acid Has a Greater Anti-tumoral Effect on Prostate Cancer Growth than Either Drug Alone.

In Vivo 2019 Jan-Feb;33(1):99-108

Flinders Centre for Innovation in Cancer, Flinders University and Medical Centre, Adelaide, South Australia.

Background/aim: The hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA) have individually shown anti-tumor effects in prostate cancer in vitro. The present study intended to investigate the efficacy of the combination of MET and VPA in prostate cancer treatment in a pre-clinical xenograft model.

Materials And Methods: Prostate cancer cell lines (LNCaP and PC-3) were inoculated under the skin of BALB/c nude mice. Read More

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http://dx.doi.org/10.21873/invivo.11445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364073PMC
April 2019
3 Reads

Look-alikes may not act alike: Gene expression regulation and cell-type-specific responses of three valproic acid analogues in the neural embryonic stem cell test (ESTn).

Toxicol Lett 2019 Mar 19;303:28-37. Epub 2018 Dec 19.

Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.

In vitro assays to assess developmental neurotoxicity of chemicals are highly desirable. The murine neural embryonic stem cell test (ESTn) can mimic parts of early differentiation of embryonic brain and may therefore be useful for this purpose. The aim of this study was to investigate whether this test is able to rank the toxic potencies of three valproic acid analogues and to study their mode of action by investigating their individual effects on four cell types: stem cells, neurons, astrocytes and neural crest cells. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.12.005DOI Listing
March 2019
9 Reads

Kidney Biopsy Findings in a Patient With Valproic Acid-Associated Fanconi Syndrome.

Pediatr Dev Pathol 2018 Dec 19:1093526618819334. Epub 2018 Dec 19.

2 Department of Pathology, Zucker School of Medicine, Hofstra University, Hempstead, New York.

A 7-year-old boy with a history of febrile illness-related epilepsy syndrome presented with proteinuria and elevated creatinine. His severe epileptic disorder has been treated since age 2 with multiple antiepileptic medications, including valproic acid. More recently, he was noted to have features of Fanconi syndrome with acidosis, hypophosphatemia, hypokalemia, glucosuria, and nephrotic-range proteinuria. Read More

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http://dx.doi.org/10.1177/1093526618819334DOI Listing
December 2018
2 Reads

Anemia secondary to the use of sodium valproate for preventing postoperative seizures in a 79-year-old man: A case report.

Medicine (Baltimore) 2018 Dec;97(50):e13626

Department of Geriatrics.

Rationale: Sodium valproate is a widely used antiepileptic drug and also used to prevent postoperative seizures in neurosurgery. Anemia caused by sodium valproate is occasionally reported and most are from pediatric patients.

Patient Concerns: We present the case of a 79-year-old man who developed anemia in the setting of a short-term sodium valproate therapy for the prevention of postoperative seizures. Read More

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http://dx.doi.org/10.1097/MD.0000000000013626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320182PMC
December 2018
3 Reads

The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism.

Mol Autism 2018 10;9:61. Epub 2018 Dec 10.

2Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, 2504 Stockton Blvd, Sacramento, CA 95817 USA.

Background: Gut microbiota has the capacity to impact the regular function of the brain, which can in turn affect the composition of microbiota. Autism spectrum disorder (ASD) patients suffer from gastrointestinal problems and experience changes in gut microbiota; however, it is not yet clear whether the change in the microbiota associated with ASD is a cause or a consequence of the disease.

Methods: We have investigated the species richness and microbial composition in a valproic acid (VPA)-induced rat model autism. Read More

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http://dx.doi.org/10.1186/s13229-018-0251-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288876PMC
January 2019
4 Reads
5.486 Impact Factor

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://dx.doi.org/10.18053/jctres.04.201801.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261533PMC
May 2018
6 Reads

A nanodelivered Vorinostat derivative is a promising oral compound for the treatment of visceral leishmaniasis.

Pharmacol Res 2019 01 29;139:375-383. Epub 2018 Nov 29.

Departamento de Parasitología, Universidad de Granada, Campus de Cartuja sn, 18011, Granada, Spain. Electronic address:

There is currently no satisfactory treatment for visceral leishmaniasis; the disease is thus in desperate need of novel drugs. The ideal candidate should be effective, safe, affordable, and administered via the oral route. Histone deacetylases (HDACs) are involved in silencing critical regulatory pathways, including pro-apoptotic programs, and represent potential therapeutic targets for pharmacological interventions. Read More

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http://dx.doi.org/10.1016/j.phrs.2018.11.039DOI Listing
January 2019
2 Reads
4.408 Impact Factor

Larval zebrafish model for studying the effects of valproic acid on neurodevelopment: An approach towards modeling autism.

J Pharmacol Toxicol Methods 2019 Jan - Feb;95:56-65. Epub 2018 Nov 27.

Drug Discovery Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Hyderabad 500078, India. Electronic address:

Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder of early onset, characterized by impaired sociability, cognitive function and stereotypies. The etiology of ASD involves a multidimensional link between genetic, neurobiological and environmental factors. Since existing, comprehensive animal models for ASD are time consuming and laborious, the need for simple, quick approaches to study subsets of ASD-associated characteristics has always been in demand for better understanding of disease. Read More

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http://dx.doi.org/10.1016/j.vascn.2018.11.006DOI Listing
March 2019
3 Reads

A Three-Dimensional Organoid Culture Model to Assess the Influence of Chemicals on Morphogenetic Fusion.

Toxicol Sci 2018 Dec;166(2):394-408

Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US EPA, Research Triangle Park, North Carolina 27711.

Embryologic development involves cell differentiation and organization events that are unique to each tissue and organ and are susceptible to developmental toxicants. Animal models are the gold standard for identifying putative teratogens, but the limited throughput of developmental toxicological studies in animals coupled with the limited concordance between animal and human teratogenicity motivates a different approach. In vitro organoid models can mimic the three-dimensional (3D) morphogenesis of developing tissues and can thus be useful tools for studying developmental toxicology. Read More

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http://dx.doi.org/10.1093/toxsci/kfy207DOI Listing
December 2018
3 Reads

Regional and sex-dependent alterations in Purkinje cell density in the valproate mouse model of autism.

Neuroreport 2019 01;30(2):82-88

Physiology of Neuronal Networks.

Neuropathological and neuroimaging studies indicate a decrease in Purkinje cell (PC) density in the cerebellum of autistic patients and rodent models of autism. Autism is far more prevalent in males than females, and sex-specific properties of PCs have been reported recently. We investigated the differential sensitivity of PCs in the valproate acid (VPA) mouse model of autism by estimating the linear density of PCs immununolabelled with calbindin in the cerebellum of males and females. Read More

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http://dx.doi.org/10.1097/WNR.0000000000001164DOI Listing
January 2019
15 Reads

Adverse Effects of Treatment with Valproic Acid during the Neonatal Period.

Neuropediatrics 2019 Feb 19;50(1):31-40. Epub 2018 Nov 19.

Service de Neurologie Pédiatrique, Hôpital des Enfants, Toulouse Cedex, France.

Introduction:  Valproic acid (VPA) is rarely used in neonatal period. In children under 2 years old, serious adverse effects are appear to be more frequent.

Aim:  The aim of our study is to report the adverse effects observed in a population of full-term newborns treated with VPA. Read More

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http://dx.doi.org/10.1055/s-0038-1676035DOI Listing
February 2019
2 Reads

Histone deacetylase inhibitors in hepatocellular carcinoma: A therapeutic perspective.

Surg Oncol 2018 Dec 30;27(4):611-618. Epub 2018 Jul 30.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA. Electronic address:

Hepatocellular carcinoma (HCC) is a major contributor to the global cancer burden. Given the current limited options to treat advanced HCC, understanding the molecular basis of HCC carcinogenesis and pinpointing druggable targets will be important to identify future HCC treatments. Epigenetic modification by inhibiting histone deacetylases (HDAC) is an emerging approach with promising results in cancer treatment. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09607404183018
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http://dx.doi.org/10.1016/j.suronc.2018.07.015DOI Listing
December 2018
17 Reads
3.270 Impact Factor

Repression of Transcriptional Activity of Forkhead Box O1 by Histone Deacetylase Inhibitors Ameliorates Hyperglycemia in Type 2 Diabetic Rats.

Int J Mol Sci 2018 Nov 9;19(11). Epub 2018 Nov 9.

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

Type 2 diabetes mellitus (T2DM) is a chronic disease manifested by hyperglycemia. It is essential to effectively control hyperglycemia to prevent complications of T2DM. Here, we hypothesize that repression of transcriptional activity of forkhead box O1 (FoxO1) via histone deacetylase inhibitors (HDACi) ameliorates hyperglycemia in T2DM rats. Read More

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http://www.mdpi.com/1422-0067/19/11/3539
Publisher Site
http://dx.doi.org/10.3390/ijms19113539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274985PMC
November 2018
15 Reads

Late toxicity in long-term survivors from a phase 2 study of concurrent radiation therapy, temozolomide and valproic acid for newly diagnosed glioblastoma.

Neurooncol Pract 2018 Nov 16;5(4):246-250. Epub 2018 Apr 16.

Radiation Oncology Branch, National Cancer Institute/NIH, Center Drive, CRC, Bethesda, MD.

Background: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor activity shown to enhance overall survival and progression free survival in patients with newly diagnosed glioblastoma (GBM). This reports on the late toxicity of the VPA/radiotherapy (RT)/temozolomide (TMZ) combination in the long-term survivors of a phase 2 study evaluating this regimen.

Methods: 37 patients with newly diagnosed GBM were initially enrolled on this trial and received combination therapy. Read More

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http://dx.doi.org/10.1093/nop/npy009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213944PMC
November 2018
14 Reads

Recurrent epileptiform discharges in the medial entorhinal cortex of kainate-treated rats are differentially sensitive to antiseizure drugs.

Epilepsia 2018 11 17;59(11):2035-2048. Epub 2018 Oct 17.

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.

Objective: Approximately 30% of patients with epilepsy are refractory to existing antiseizure drugs (ASDs). Given that the properties of the central nervous systems of these patients are likely to be altered due to their epilepsy, tissues from rodents that have undergone epileptogenesis might provide a therapeutically relevant disease substrate for identifying compounds capable of attenuating pharmacoresistant seizures. To facilitate the development of such a model, this study describes the effects of classical glutamate receptor antagonists and 20 ASDs on recurrent epileptiform discharges (REDs) in brain slices derived from the kainate-induced status epilepticus model of temporal lobe epilepsy (KA-rats). Read More

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http://dx.doi.org/10.1111/epi.14563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215509PMC
November 2018
6 Reads

Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway.

Life Sci 2018 Nov 6;212:261-266. Epub 2018 Oct 6.

Department of pharmacology and toxicology, faculty of pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt.

Aim: The current study evaluates the anticonvulsant effect of valproic acid (VPA) alone or combined with low dose γ-irradiation (LDR) against pentylenetetrazol-induced convulsions in rats.

Material And Methods: Five groups of rats were used, group I served as normal control, group II served as PTZ- control and the other three groups were pretreated with single LDR(o.5 Gy), VPA(150 mg/kg i. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00243205183062
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http://dx.doi.org/10.1016/j.lfs.2018.10.007DOI Listing
November 2018
7 Reads

Agmatine protects against sodium valproate-induced hepatic injury in mice via modulation of nuclear factor-κB/inducible nitric oxide synthetase pathway.

J Biochem Mol Toxicol 2018 Dec 1;32(12):e22227. Epub 2018 Oct 1.

Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia.

Valproate is a widely used drug against epilepsy and several other neurological disorders although it has deleterious hepatotoxic side effects. The current study was designed to test if agmatine as nitric oxide modulator has protective effects against valproate-induced hepatic injury. Male Swiss albino mice were treated with sodium valproate (SVP) with or without agmatine for 7 days. Read More

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http://doi.wiley.com/10.1002/jbt.22227
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http://dx.doi.org/10.1002/jbt.22227DOI Listing
December 2018
69 Reads
1.925 Impact Factor

Variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma POLG1 are not associated with increased risk for valproate-induced hepatotoxicity or pancreatic toxicity: A retrospective cohort study of patients with epilepsy.

Epilepsia 2018 11 26;59(11):2125-2136. Epub 2018 Sep 26.

Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology, University of Oulu, Oulu, Finland.

Objective: Previous studies have suggested that heterozygous variants p.Q1236H and p.E1143G in mitochondrial DNA polymerase gamma (POLG1) increase the risk for liver injury for patients on valproate (VPA) therapy. Read More

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http://dx.doi.org/10.1111/epi.14568DOI Listing
November 2018
5 Reads

Deep Brain Stimulation Modified Autism-Like Deficits via the Serotonin System in a Valproic Acid-Induced Rat Model.

Int J Mol Sci 2018 Sep 19;19(9). Epub 2018 Sep 19.

Department and Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.

Deep brain stimulation (DBS) is known to be a promising treatment for resistant depression, which acts via the serotonin (5-hydroxytryptamine, 5-HT) system in the infralimbic prefrontal cortex (ILPFC). Previous study revealed that dysfunction of brain 5-HT homeostasis is related to a valproate (VPA)-induced rat autism spectrum disorder (ASD) model. Whether ILPFC DBS rescues deficits in VPA-induced offspring through the 5-HT system is not known. Read More

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http://dx.doi.org/10.3390/ijms19092840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164279PMC
September 2018
4 Reads

Lamotrigine-Valproic Acid Interaction Leading to Stevens-Johnson Syndrome.

Case Rep Med 2018 29;2018:5371854. Epub 2018 Aug 29.

Genia-Genetics Molecular Laboratory, Bulevar General Artigas 922, 11300 Montevideo, Uruguay.

Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary from transient mild rash to Stevens-Johnson syndrome (SJS), which can be fatal mainly when LTG is coadministered with valproic acid (VPA). Read More

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http://dx.doi.org/10.1155/2018/5371854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136509PMC
August 2018
6 Reads

Intranasally administered pitavastatin ameliorates pentylenetetrazol-induced neuroinflammation, oxidative stress and cognitive dysfunction.

Life Sci 2018 Oct 15;211:172-181. Epub 2018 Sep 15.

Om Bioscience and Pharma College, Roorkee-Haridwar, Uttarakhand 249405, India. Electronic address:

Aim: The present study aimed to evaluate the neuroprotective potential of intranasally administered pitavastatin in the PTZ-induced kindling model.

Materials And Methods: Subconvulsant dose of PTZ (35 mg/kg, i.p) was administered on an alternate day until the development of kindling. Read More

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http://dx.doi.org/10.1016/j.lfs.2018.09.025DOI Listing
October 2018
2 Reads
2.700 Impact Factor

[Valproic acid toxicity due to misinterpretation of plasma levels: increase in unbound fraction caused by hypoalbuminaemia and renal dysfunction].

Ned Tijdschr Geneeskd 2018 08 16;162. Epub 2018 Aug 16.

VUmc, afd. Ziekenhuispsychiatrie, Amsterdam.

Background: Valproic acid is one of the most widely prescribed drugs for the treatment of epilepsy and bipolar disorder. As only the unbound fraction of a medicinal product is pharmacologically active, in some strong protein-bound psychotropic drugs such as valproic acid and phenytoin, a rise in this fraction can lead to severe toxicity.

Case Description: A 65-year-old male with a type 1 bipolar disorder developed a number of neurological symptoms including sluggishness, muscle weakness, difficulty in walking and disorders of micturition after his mood stabiliser was changed to valproic acid. Read More

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August 2018
3 Reads

Therapeutic drug monitoring of valproic acid.

Pak J Pharm Sci 2018 Jul;31(4(Special)):1773-1776

Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.

The unpredictable and unfavorable connection of dose and plasma concentration of valproic acid supports the necessity to regularly measure its plasma concentration. The present study is drug monitoring of valproic acid and comparative evaluation of therapeutic monitoring results of valproic acid for assessment of clinical response, safety and toxicity in different age and gender groups of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of valproic acid in various sub-groups of epileptic patients for enhancing the safety and minimizing the toxicity of valproic acid. Read More

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July 2018
7 Reads

Early Behavioral Alterations and Increased Expression of Endogenous Retroviruses Are Inherited Across Generations in Mice Prenatally Exposed to Valproic Acid.

Mol Neurobiol 2019 May 7;56(5):3736-3750. Epub 2018 Sep 7.

Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161, Rome, Italy.

Prenatal treatment with the antiepileptic drug valproic acid (VPA) is associated with a significant risk of somatic anomalies, neurodevelopmental delays, and 7-10× increase in the incidence of autism spectrum disorders (ASD) in children. Rodents exposed to VPA in pregnancy show birth defects, deficits in neurodevelopment, and cognitive/social anomalies resembling those of ASD children. Mechanisms of VPA neurobehavioral toxicity are still unclear but as VPA is a non-selective inhibitor of histone deacetylases, epigenetic modifications are likely involved. Read More

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http://dx.doi.org/10.1007/s12035-018-1328-xDOI Listing
May 2019
8 Reads

Attenuating M-current suppression in vivo by a mutant Kcnq2 gene knock-in reduces seizure burden and prevents status epilepticus-induced neuronal death and epileptogenesis.

Epilepsia 2018 10 26;59(10):1908-1918. Epub 2018 Aug 26.

Department of Pharmacology, University of California, Irvine, Irvine, California.

Objectives: The M-current is a low-threshold voltage-gated potassium current generated by Kv7 subunits that regulates neural excitation. It is important to note that M-current suppression, induced by activation of Gq-coupled neurotransmitter receptors, can dynamically regulate the threshold of action-potential firing and firing frequency. Here we sought to directly examine whether M-current suppression is involved in seizures and epileptogenesis. Read More

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http://doi.wiley.com/10.1111/epi.14541
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http://dx.doi.org/10.1111/epi.14541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204291PMC
October 2018
11 Reads

New regulations to cut valproate-exposed pregnancies.

Lancet 2018 08 9;392(10146):458-460. Epub 2018 Aug 9.

Department of Neurology, King's College Hospital, London, UK.

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http://dx.doi.org/10.1016/S0140-6736(18)31672-6DOI Listing
August 2018
11 Reads

Effect of valproic acid on survival in glioblastoma: A prospective single-arm study.

South Asian J Cancer 2018 Jul-Sep;7(3):159-162

Department of Neurosurgery, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India.

Background: Retrospective evidence suggests that valproic acid (VPA), an antiepileptic drug, is associated with improved outcomes in glioblastoma. The exact mechanism of interaction of VPA with radiation and temozolomide (TMZ) is still unclear. Laboratory studies show that VPA can enhance tumor cell kill while at the same time protect the normal neural tissue. Read More

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http://dx.doi.org/10.4103/sajc.sajc_188_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069328PMC
August 2018
10 Reads

Avoid valproate in patients with IARS2 mutations.

Brain Dev 2019 Jan 9;41(1):121. Epub 2018 Aug 9.

University of Tunis El Manar and Genomics Platform, Pasteur Institute of Tunis, Tunisia.

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http://dx.doi.org/10.1016/j.braindev.2018.07.019DOI Listing
January 2019
4 Reads

Valproic acid is protective in cellular and worm models of oculopharyngeal muscular dystrophy.

Neurology 2018 Aug 13;91(6):e551-e561. Epub 2018 Jul 13.

From the Montreal Neurological Institute and Hospital (A.A.-B., P.D., G.R.), Ingram School of Nursing, Faculty of Medicine (S.R.), and Department of Neurology and Neurosurgery (G.R.), McGill University, Montreal; CHUM Research Center (A.P.), Montreal; Department of Neuroscience (A.P.), and Ophthalmology Research Hôpital Maisonneuve Rosemont, Laboratoire de Isabelle Brunette (J.L.), University of Montreal; Neuromuscular Group (B.B.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; and Brain C-lab (C.N.), Institute of Biology Paris-Seine, CNRS UMR 8256 Biology of Adaptation & Aging, University Pierre and Marie Curie, Paris, France.

Objective: To explore valproic acid (VPA) as a potentially beneficial drug in cellular and worm models of oculopharyngeal muscular dystrophy (OPMD).

Methods: Using a combination of live cell imaging and biochemical measures, we evaluated the potential protective effect of VPA in a stable C2C12 muscle cell model of OPMD, in lymphoblastoid cell lines derived from patients with OPMD and in a transgenic OPMD model expressing human mutant PABPN1.

Results: We demonstrated that VPA protects against the toxicity of mutant PABPN1. Read More

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http://dx.doi.org/10.1212/WNL.0000000000005942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105050PMC
August 2018
24 Reads

Leptin and camel milk abate oxidative stress status, genotoxicity induced in valproic acid rat model of autism.

Int J Immunopathol Pharmacol 2018 Jan-Dec;32:2058738418785514

2 Oral Biology Department, Faculty Oral and Dental Medicine, Cairo University, Egypt.

The aspect of treatment of autistic behaviour was investigated using valproic acid rat model of pregnant female rats. Two main groups (10 male rats/group) were treated for 6 days and then divided into six subgroups. The first group of normal rats was divided into three subgroups: (A) - control group, (B) - treated with camel milk (CAM; 2 mL/p. Read More

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http://dx.doi.org/10.1177/2058738418785514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047246PMC
December 2018
6 Reads

Valproic acid attenuates Aβ-induced neurotoxicity in PC12 cells through suppression of mitochondria-mediated apoptotic pathway.

Biomed Pharmacother 2018 Oct 26;106:77-82. Epub 2018 Jun 26.

Department of Neurology, No.1 People's Hospital of Jining City, Jining, Shandong, China. Electronic address:

Aggregation of amyloid-β (Aβ) peptides is a pathological hallmark of Alzheimer's disease (AD). The purpose of the present study was to identify the protective role of valproic acid (VPA) against β-amyloid protein fragment 25-35 (Aβ)-caused neurotoxicity in PC12 cells. Different doses of VPA was added to cultures of differentiated PC12 cells, 1 h before Aβ. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.06.080DOI Listing
October 2018
9 Reads

Valproate serum concentrations in patients with hypoalbuminemia and medical complications.

Ment Health Clin 2017 Jan 23;7(1):13-15. Epub 2018 Mar 23.

Assistant Professor, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina.

Introduction: Valproic acid (VPA) and its derivatives are highly protein bound with free fraction increasing with dose and serum concentration. Consensus guidelines regarding dose adjustment for hypoalbuminemia are not available.

Methods: A literature search was performed using PubMed to identify articles with the following key terms: "valproate," "valproic acid," "protein binding," "albumin," and "hypoalbuminemia. Read More

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http://dx.doi.org/10.9740/mhc.2017.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007656PMC
January 2017
2 Reads

Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment.

Mol Autism 2018 14;9:36. Epub 2018 Jun 14.

Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, Buenos Aires, Argentina.

Background: Autism spectrum disorder (ASD) is characterized by impaired social interactions and repetitive patterns of behavior. Symptoms appear in early life and persist throughout adulthood. Early social stimulation can help reverse some of the symptoms, but the biological mechanisms of these therapies are unknown. Read More

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http://dx.doi.org/10.1186/s13229-018-0221-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001054PMC
October 2018
7 Reads

Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma.

Clin Epigenetics 2018 18;10:79. Epub 2018 Jun 18.

CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.

Background: Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. Read More

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https://clinicalepigeneticsjournal.biomedcentral.com/article
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http://dx.doi.org/10.1186/s13148-018-0517-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006850PMC
June 2018
21 Reads

The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy.

Mol Neurobiol 2019 Feb 7;56(2):1233-1247. Epub 2018 Jun 7.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i. Read More

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http://dx.doi.org/10.1007/s12035-018-1121-xDOI Listing
February 2019
18 Reads
5.140 Impact Factor

Ether-phosphatidylcholine characterized by consolidated plasma and liver lipidomics is a predictive biomarker for valproic acid-induced hepatic steatosis.

J Toxicol Sci 2018 ;43(6):395-405

Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO Inc.

Valproic acid (VPA) is known to induce hepatic steatosis due to mitochondrial toxicity in rodents and humans. In the present study, we administered VPA to SD rats for 3 or 14 days at 250 and 500 mg/kg and then performed lipidomics analysis to reveal VPA-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. VPA induced hepatic steatosis at the high dose level without any degenerative changes in the liver on day 4 (after 3 days dosing) and at the low dose level on day 15 (after 14 days dosing). Read More

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http://dx.doi.org/10.2131/jts.43.395DOI Listing
August 2018
5 Reads

Is post exposure prevention of teratogenic damage possible: Studies on diabetes, valproic acid, alcohol and anti folates in pregnancy: Animal studies with reflection to human.

Reprod Toxicol 2018 09 31;80:92-104. Epub 2018 May 31.

Hebrew University Hadassah Medical School, Jerusalem, Israel.

We discuss the possibilities to prevent the post-exposure teratogenic effects of several teratogens: valproic acid (VPA), diabetes and alcohol. Co-administration of folic acid with VPA reduced the rate of Neural Tube Defects (NTD) and other anomalies in rodents, but apparently not in pregnant women. Antioxidants or the methyl donor S-adenosyl methionine prevented Autism Spectrum Disorder (ASD) like behavior in mice and rats. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08906238183010
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http://dx.doi.org/10.1016/j.reprotox.2018.05.006DOI Listing
September 2018
14 Reads

Modulatory effects of some natural products on hepatotoxicity induced by combination of sodium valproate and paracetamol in rats.

J Biochem Mol Toxicol 2018 May 25:e22162. Epub 2018 May 25.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

Possible hepatoprotective effect of Curcuma longa and/or Nigella sativa against hepatotoxicity induced by coadministration of sodium valproate (SV) and paracetamol was studied. Rats were divided into 10 groups, control groups 1, 2, 3, and 4 received vehicles, C. longa (200 mg/kg, p. Read More

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http://dx.doi.org/10.1002/jbt.22162DOI Listing
May 2018
7 Reads
1.925 Impact Factor

Valproic acid attenuates manganese-induced reduction in expression of GLT-1 and GLAST with concomitant changes in murine dopaminergic neurotoxicity.

Neurotoxicology 2018 07 18;67:112-120. Epub 2018 May 18.

Department of Pharmaceutical Sciences, College of Pharmacy, Florida A&M University, Tallahassee, FL, 32301, United States. Electronic address:

Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models. Read More

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http://dx.doi.org/10.1016/j.neuro.2018.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441963PMC
July 2018
1 Read

A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies.

Toxicol Lett 2018 Sep 21;294:51-60. Epub 2018 May 21.

iBB - Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Lisbon Campus, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. Electronic address:

Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.05.018DOI Listing
September 2018
8 Reads

Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice.

J Appl Toxicol 2018 Sep 16;38(9):1215-1223. Epub 2018 May 16.

Department of Pharmacology, Laboratory of Physiology and Pharmacology of Reproduction, Universidade Federal de Goiás, Goiânia, GO, Brazil.

Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. Read More

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http://dx.doi.org/10.1002/jat.3631DOI Listing
September 2018
8 Reads