1,873 results match your criteria Toxicity Valproate

Therapeutic Use of Valproic Acid and All-Trans Retinoic Acid in Acute Myeloid Leukemia-Literature Review and Discussion of Possible Use in Relapse after Allogeneic Stem Cell Transplantation.

Pharmaceuticals (Basel) 2021 May 2;14(5). Epub 2021 May 2.

Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway.

Even though allogeneic stem cell transplantation is the most intensive treatment for acute myeloid leukemia (AML), chemo-resistant leukemia relapse is still one of the most common causes of death for these patients, as is transplant-related mortality, i.e., graft versus host disease, infections, and organ damage. Read More

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Taurine attenuates valproic acid-induced hepatotoxicity via modulation of RIPK1/RIPK3/MLKL-mediated necroptosis signaling in mice.

Mol Biol Rep 2021 May 25. Epub 2021 May 25.

Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Valproic acid (VPA) is known as a common drug in seizure and bipolar disorders treatment. Hepatotoxicity is the most important complication of VPA. Taurine (Tau), an amino acid, has antioxidant effects. Read More

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Which treatment strategy in patients with epilepsy with focal seizures uncontrolled by the first anti-seizure medication?

Epilepsy Behav 2021 May 13;121(Pt A):108031. Epub 2021 May 13.

Department of Neurology, Hospital of Merano (SABES-ASDAA), Merano-Meran, Italy.

There is no definite proven or accepted strategy in the management of patients with focal epilepsy uncontrolled by the first anti-seizure medication (ASM). Clinical studies failed to find a significant difference in efficacy or tolerability between alternative monotherapy and/or adjunctive therapy in these patients. A second ASM is often added, the efficacy of the combination is assessed, and the dose of the first drug can be gradually reduced and withdrawn. Read More

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The long-term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy.

Neuropsychopharmacol Rep 2021 Jun 5;41(2):260-264. Epub 2021 May 5.

Department of Psychiatry, Juntendo Koshigaya Hospital, Saitama, Japan.

Aim: In pregnant women with epilepsy, it is essential to balance maternal safety and the potential teratogenicity of anticonvulsants. Recently, growing evidence has indicated that valproic acid (VPA) can produce postnatal congenital malformations and impair cognitive function. However, the mechanisms underlying cognitive dysfunction in long-term prognoses remain unclear. Read More

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PXR-mediated expression of FABP4 promotes valproate-induced lipid accumulation in HepG2 cells.

Toxicol Lett 2021 Aug 24;346:47-56. Epub 2021 Apr 24.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, 450052, China. Electronic address:

Valproate (valproic acid, VPA) is widely used in the therapy of epilepsy. However, adverse effect like hepatic steatosis has been reported in patients receiving VPA treatment. But whether nuclear receptor pregnane X receptor (PXR) and fatty acid binding protein 4 (FABP4) are involved in the regulation of VPA-induced steatosis or not is still unknown. Read More

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Chronic serotonin syndrome: A retrospective study.

World J Psychiatry 2021 Apr 19;11(4):124-132. Epub 2021 Apr 19.

Department of Medicine, Smt. B.K. Shah Medical Institute and Research Centre, Sumandeep Vdyapeeth, Vadodara 391760, India.

Background: Serotonin syndrome (SS) is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin. Very limited information is available about chronic SS.

Aim: To evaluate the epidemiological, clinical, and other aspects of the insidious onset SS. Read More

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Managing valproic acid toxicity-related hyperammonaemia: an unpredicted course.

BMJ Case Rep 2021 Apr 19;14(4). Epub 2021 Apr 19.

Department of Pharmacy, Mayo Clinic Rochester, Rochester, Minnesota, USA.

A 20-year-old woman presented following an intentional overdose of valproic acid. Use of valproic acid, either acute or chronic, can result in hyperammonaemia. Mild hyperammonaemia with chronic use is mostly asymptomatic but can also present with concern for encephalopathy. Read More

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The Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51.

Front Oncol 2021 25;11:646256. Epub 2021 Mar 25.

Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0. Read More

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HIV Post Exposure Prophylaxis and Risk of Relapse in Adolescent With Bipolar Illness and Psychopharmacologic Challenges.

Mayank Gupta

Cureus 2021 Mar 9;13(3):e13777. Epub 2021 Mar 9.

Psychiatry, Lake Erie College of Osteopathic Medicine, Erie, USA.

Bipolar disorder (BD) in adolescents is associated with risky behaviors, including high risk for sexually transmitted infections. When exposed, post exposure prophylaxis (PEP) is recommended within 72 hours for a period of 28 days. The medications used for PEP are known to have common neuropsychiatric side effects, renal toxicity and risk of hepatic injury. Read More

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Monitoring for valproate and phenytoin toxicity in hypoalbuminaemia: A retrospective cohort study.

Br J Clin Pharmacol 2021 Apr 9. Epub 2021 Apr 9.

Faculty of Medicine, University of Queensland, Brisbane, Australia.

Aims: Equations to calculate albumin-adjusted total concentrations have been validated to correlate with measured free concentrations for both phenytoin and valproate, but there is a lack of data to assess correlation with clinical outcomes. We aimed to assess the association of hypoalbuminaemia and albumin-adjusted total concentrations with concentration-dependent toxicity for phenytoin and valproate and review the impact on management decisions following concentration monitoring in hypoalbuminaemia.

Methods: Patients undergoing concentration monitoring for phenytoin or valproate between January and December 2018 were included. Read More

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Neuroprotection by delayed triple therapy following sarin nerve agent insult in the rat.

Toxicol Appl Pharmacol 2021 05 3;419:115519. Epub 2021 Apr 3.

Department of Pharmacology, Israel Institute for Biological, Chemical and Environmental Sciences, Ness-Ziona 74100, Israel. Electronic address:

The development of refractory status epilepticus (SE) induced by sarin intoxication presents a therapeutic challenge. In our current research we evaluate the efficacy of a delayed combined triple treatment in ending the abnormal epileptiform seizure activity (ESA) and the ensuing of long-term neuronal insult. SE was induced in male Sprague-Dawley rats by exposure to 1. Read More

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A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children.

Epileptic Disord 2021 Apr;23(2):229-256

Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.

Comorbidity between epilepsy and infectious diseases in children is frequent. Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity. All potential DDIs between ASMs and antimicrobial agents used in children were identified through consultation of drug compendia. Read More

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Emerging mechanisms of valproic acid-induced neurotoxic events in autism and its implications for pharmacological treatment.

Biomed Pharmacother 2021 May 16;137:111322. Epub 2021 Feb 16.

Key Lab of Cardiovascular and Cerebrovascular Medicine, Drug Target and Drug Discovery Center, School of Pharmacy, Nanjing Medical University, Nanjing, China; Institute of Brain Sciences, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Autism spectrum disorder (ASD) is a sort of mental disorder marked by deficits in cognitive and communication abilities. To date no effective cure for this pernicious disease has been available. Valproic acid (VPA) is a broad-spectrum, antiepileptic drug, and it is also a potent teratogen. Read More

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New Avenues for Treatment and Prevention of Drug-Induced Steatosis and Steatohepatitis: Much More Than Antioxidants.

Adv Ther 2021 05 24;38(5):2094-2113. Epub 2021 Mar 24.

Department of Clinical Medicine and Surgery, "Federico II" University Medical School of Naples, Naples, Italy.

Drug-induced lipid accumulation in the liver may induce two clinically relevant conditions, drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH). The list of drugs that may cause DIS or DISH is long and heterogeneous and includes therapeutically relevant molecules that cannot be easily replaced by less hepatotoxic medicines, therefore making specific strategies necessary for DIS/DISH prevention or treatment. For years, the only available tools to achieve these goals have been antioxidant drugs and free radical scavengers, which counteract drug-induced mitochondrial dysfunction but, unfortunately, have only limited efficacy. Read More

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A systematic review of second line therapies in toxic seizures.

Clin Toxicol (Phila) 2021 Jun 23;59(6):451-456. Epub 2021 Mar 23.

New Mexico Poison and Drug Information Center, Albuquerque, NM, USA.

Background: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. Read More

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First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid.

Epilepsia 2021 May 18;62(5):1119-1129. Epub 2021 Mar 18.

Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.

Objective: This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.

Methods: In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Read More

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Brain and plasma amino acid concentration in infant rats prenatally exposed to valproic acid.

An Acad Bras Cienc 2021 15;93(2):e20190861. Epub 2021 Mar 15.

Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos, s/n, Col. Unidad del Bosque, 91010 Xalapa, Veracruz, México.

Autism spectrum disorder is associated with alterations in GABAergic and glutamatergic neurotransmission. Here, we aimed to determine the concentration of GABA, glutamate, glutamine, aspartate, taurine, and glycine in brain tissue and plasma of rats prenatally exposed to valproic acid (VPA), a well-characterized experimental model of autism. Pregnant rats were injected with VPA (600mg/Kg) during the twelfth-embryonic-day. Read More

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Evaluation of transporter expression in HK-2 cells after exposure to free and ester-bound 3-MCPD.

Toxicol Rep 2021 23;8:436-442. Epub 2021 Feb 23.

U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DT), Laurel, MD, 20817, United States.

3-Monochloropropane-1,2-diol (3-MCPD) is a food processing contaminant in some infant formula products and other foods in the United States. Although rodent studies have demonstrated that 3-MCPD and its palmitic esters have the potential to induce nephrotoxicity, our recent human cell culture studies using the human renal proximal tubule cell line HK-2 have not strongly supported this finding. Considering this disparity, we sought to examine whether changes in transporter gene expression on proximal tubule cells could be modulated by these compounds and allow us to glean mechanistic information on a possible indirect path to proximal tubule injury . Read More

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February 2021

Thinking out of the box: management of valproic acid toxicity with carbapenems.

BMJ Case Rep 2021 Mar 10;14(3). Epub 2021 Mar 10.

Pulmonary & Critical Care Medicine, Nassau University Medical Center, East Meadow, New York, USA.

Valproic acid (VPA) is commonly used medication to treat seizure disorder and as prophylaxis for bipolar disorder. Acute VPA toxicity can cause varied symptoms ranging from mild drowsiness to severe cerebral oedema and coma. The therapeutic level of VPA is around 50-100 µg/mL and most of it is protein bound. Read More

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Creating a human-induced pluripotent stem cell-based NKX2.5 reporter gene assay for developmental toxicity testing.

Arch Toxicol 2021 05 4;95(5):1659-1670. Epub 2021 Mar 4.

National Food Institute, Technical University of Denmark, Kemitorvet, Building 201, 2800, Kongens Lyngby, Denmark.

To test large numbers of chemicals for developmental toxicity, rapid in vitro tests with standardized readouts for automated data acquisition are needed. However, the most widely used assay, the embryonic stem cell test, relies on the counting of beating embryoid bodies by visual inspection, which is laborious and time consuming. We previously developed the PluriBeat assay based on differentiation of human induced pluripotent stem cells (hiPSC) that we demonstrated to be predictive for known teratogens at relevant concentrations using the readout of beating cardiomyocytes. Read More

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Knowledge of epilepsy among German pharmacists.

Epilepsy Res 2021 May 17;172:106587. Epub 2021 Feb 17.

Neuropaediatrics, University Hospital for Children and Adolescents, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany. Electronic address:

Problem: Pharmacists can have a large impact on attitude, acceptance and adherence in patients with long-term conditions. They should be able to give appropriate advice.

Methods: We invited pharmacists in Mecklenburg-Vorpommern and Saxony, Germany, to complete a questionnaire mainly containing multiple-choice-questions. Read More

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Toxicity of psychotropic drugs in patients with COVID-19: A systematic review.

Gen Hosp Psychiatry 2021 May-Jun;70:1-9. Epub 2021 Feb 18.

Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, 2, Chemin du Petit-Bel-Air, CH-1226 Thonex, Switzerland.

Objective: Due to the global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), guidance for the use of psychotropic drugs in this context is necessary. We aimed to review clinical evidence regarding the potential toxicity of psychiatric medications in the context of SARS-CoV-2 infection.

Methods: A systematic search for all types of empirical studies and reviews in a broad set of electronic databases and trial registries was conducted up to the 15th of August 2020. Read More

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Valproate-Induced Hyperammonemic Encephalopathy Following Accidental Ingestion in a Toddler.

J Pediatr Pharmacol Ther 2021 15;26(2):210-212. Epub 2021 Feb 15.

Clinical manifestations of valproic acid (VPA) toxicity can range from just mild confusion and drowsiness to serious encephalopathy, leading to depressed sensorium and even coma and death. The exact cause(s) of how VPA influences the integrity of brain function remains unknown. Nevertheless, several mechanisms have been postulated including a surge in the blood ammonia concentration. Read More

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February 2021

Pseudosubarachnoid hemorrhage: A systematic review of causes, diagnostic modalities, and outcomes in patients who present with pseudosubarachnoid hemorrhage.

Surg Neurol Int 2021 20;12:29. Epub 2021 Jan 20.

Department Neurology, University of Chicago, Chicago, Illinois, United States.

Background: Patients with computed tomography (CT) findings consistent with subarachnoid hemorrhage without evidence of hemorrhage following autopsy or cerebrospinal fluid testing are termed to have pseudosubarachnoid hemorrhage (pSAH).

Methods: A systematic review of literature was conducted based on the preferred reporting items for systematic reviews and meta-analysis statement. Studies were evaluated for associated cause of pSAH, imaging modality used in assessment, method of confirmatory testing, and clinical outcome. Read More

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January 2021

A quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases.

Toxicol Lett 2021 May 10;342:20-25. Epub 2021 Feb 10.

Institute of Biology Leiden, Leiden University, the Netherlands. Electronic address:

Many bony features of the face develop from endochondral ossification of preexisting collagen-rich cartilage structures. The proper development of these cartilage structures is essential to the morphological formation of the face. The developmental programs governing the formation of the pre-bone facial cartilages are sensitive to chemical compounds that disturb histone acetylation patterns and chromatin structure. Read More

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Perinatal exposure to BDE-47 exacerbated autistic-like behaviors and impairments of dendritic development in a valproic acid-induced rat model of autism.

Ecotoxicol Environ Saf 2021 Apr 4;212:112000. Epub 2021 Feb 4.

Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China. Electronic address:

Perinatal exposure to polybrominated diphenyl ethers (PBDEs) may be a potential risk factor for autism spectrum disorders (ASD). BDE-47 is one of the most common PBDEs and poses serious health hazards on the central nervous system (CNS). However, effects of perinatal exposure to BDE-47 on social behaviors and the potential mechanisms are largely unexplored. Read More

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Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency.

Brain Dev 2021 May 3;43(5):657-660. Epub 2021 Feb 3.

Department of Pediatrics, School of Medicine, Tokyo Women's Medical University, Japan.

Background: Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid β-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis.

Case Report: An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day. Read More

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Multistate models of developmental toxicity: Application to valproic acid-induced malformations in the zebrafish embryo.

Toxicol Appl Pharmacol 2021 03 30;414:115424. Epub 2021 Jan 30.

CERTARA UK Limited, Simcyp Division, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, United Kingdom. Electronic address:

For the determination of acute toxicity of chemicals in zebrafish (Danio rerio) embryos, the OECD test guideline 236, relative to the Fish Embryo Toxicity Test (FET), stipulates a dose-response analysis of four lethal core endpoints and a quantitative characterization of abnormalities including their time-dependency. Routinely, the data are analyzed at the different observation times separately. However, observations at a given time strongly depend on the previous effects and should be analyzed jointly with them. Read More

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Pergularia daemia alters epileptogenesis and attenuates cognitive impairment in kainate-treated mice: Insight into anti-inflammatory mechanisms.

Epilepsy Behav 2021 02 9;115:107707. Epub 2021 Jan 9.

Department of Biological Sciences, Faculty of Science, University of Maroua, P.O. Box 52, Maroua, Cameroon. Electronic address:

Background: About 60% of temporal lobe epilepsies are drug resistant. Thus, medicinal plants are sources of new antiepileptic drugs. Pergularia daemia is used in Cameroon to treat pain, fever, arthritis, infections, and temporal lobe epilepsy. Read More

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February 2021

Mutations Are Probably Rare in the Han Chinese Population.

Chin Med Sci J 2020 Dec;35(4):350-356

Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.

Objective Mutations in polymerase gamma gene ( are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. Read More

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December 2020