2,003 results match your criteria Toxicity Valproate


Comprehensive Analysis of Metabolic Changes in Male Mice Exposed to Sodium Valproate Based on GC-MS Analysis.

Drug Des Devel Ther 2022 17;16:1915-1930. Epub 2022 Jun 17.

Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, People's Republic of China.

Purpose: Sodium valproate (VPA) is the most widely used broad-spectrum antiepileptic first-line drug in clinical practice and is effective against various types of epilepsy. However, VPA can induce severe cardiotoxicity, nephrotoxicity, hepatotoxicity, and neurotoxicity, which limits its use. Metabolomic studies of VPA-induced toxicity have focused primarily on changes in serum and urine metabolites but have not evaluated changes in major organs or tissues. Read More

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Low trifloxystrobin-tebuconazole concentrations induce cardiac and developmental toxicity in zebrafish by regulating notch mediated-oxidative stress generation.

Ecotoxicol Environ Saf 2022 Jun 14;241:113752. Epub 2022 Jun 14.

Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Affiliated Hospital of Jinggangshan University, College of life sciences, Jinggangshan University, Ji'an 343009, China. Electronic address:

Trifloxystrobin-tebuconazole (TFS-TBZ) is a novel, broad-spectrum fungicide that has been frequently detected in both the environment and agricultural products. However, its adverse effects on aquatic organisms remain unknown. In this study, the adverse effects of ecologically relevant TFS-TBZ concentrations (i. Read More

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Evaluation of the inhibitory potential of Valproic acid against histone deacetylase of and computational studies of Valproic acid derivatives.

J Biomol Struct Dyn 2022 Jun 15:1-18. Epub 2022 Jun 15.

Computational Biology & Biotechnology Laboratory, Department of Botany, Soban Singh Jeena University, Almora, Uttarakhand, India.

Valproic acid (VA) is a proven inhibitor of human histone deacetylases (HDACs). The homogenous HDAC has been associated with all major human parasitic pathogens and hence, it has been considered an attractive drug target for anti-leishmanial therapy. To assist in drug design endeavors for HDACs, an in- study has been presented to investigate the VA inhibition on HDAC (HDAC). Read More

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Neuronal differentiation pathways and compound-induced developmental neurotoxicity in the human neural progenitor cell test (hNPT) revealed by RNA-seq.

Chemosphere 2022 Oct 11;304:135298. Epub 2022 Jun 11.

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

There is an increased awareness that the use of animals for compound-induced developmental neurotoxicity (DNT) testing has limitations. Animal-free innovations, especially the ones based on human stem cell-based models are pivotal in studying DNT since they can mimic processes relevant to human brain development. Here we present the human neural progenitor test (hNPT), a 10-day protocol in which neural progenitor cells differentiate into a neuron-astrocyte co-culture. Read More

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October 2022

Enhanced antitumor activity of combined methotrexate and histone deacetylase inhibitor valproic acid on mammary cancer in vitro and in vivo.

Can J Physiol Pharmacol 2022 Jun 9. Epub 2022 Jun 9.

Cairo University Faculty of Pharmacy, 110154, Pharmacology and Toxicology, Cairo, Egypt;

Histone deacetylase inhibitors (HDACIs) act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is an HDACI that shows promising chemotherapeutic effect in several tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of mammary cancer cells and its enhancing effect with methotrexate (MTX) in vitro and in vivo. Read More

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Folic Acid Rescues Valproic Acid-Induced Morphogenesis Inhibition in Neural Rosettes Derived From Human Pluripotent Stem Cells.

Front Cell Neurosci 2022 16;16:888152. Epub 2022 May 16.

Department of Prenatal Diagnosis, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

The ability of human pluripotent stem cells (hPSCs) to specialize in neuroepithelial tissue makes them ideal candidates for use in the disease models of neural tube defects. In this study, we cultured hPSCs in suspension with modified neural induction method, and immunostaining was applied to detect important markers associated with cell fate and morphogenesis to verify the establishment of the neural tube model . We carried out the drug experiments to further investigate the toxicity of valproic acid (VPA) exposure and the potential protective effect of folic acid (FA). Read More

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Critical Evaluation of Valproic Acid-Induced Rodent Models of Autism: Current and Future Perspectives.

J Mol Neurosci 2022 Jun 30;72(6):1259-1273. Epub 2022 May 30.

Cell and Molecular Biology Lab, Department of Zoology, Panjab University, Chandigarh, 160014, India.

Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism. But, to date, its validation, suitability, and applicability as a well defining autistic model are still questionable. Previous research efforts highlighted that this model shows various core defining features of autism and related pathways, hence it is very necessary to explore its authenticity as a well-suited model for autism. Read More

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Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature.

J Clin Med 2022 May 18;11(10). Epub 2022 May 18.

Border Biomedical Research Center, University of Texas at El Paso (UTEP), El Paso, TX 79968, USA.

We report a retrospective case series of six Hispanic children with tumors treated with metronomic chemotherapy. The six cases comprised one rhabdoid tumor of the kidney, one ependymoma, two medulloblastomas, one neuroblastoma, and a type II neurocytoma of the spine. Treatment included oral cyclophosphamide daily for 21 days alternating with oral etoposide daily for 21 days in a backbone of daily valproic acid and celecoxib. Read More

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Evaluation of mitochondrial oxidative toxicity in mammalian cardiomyocytes by determining the highly reproducible and reliable increase in mitochondrial superoxides after exposure to therapeutic drugs.

Toxicol In Vitro 2022 May 23;83:105393. Epub 2022 May 23.

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. Electronic address:

Mitochondria are important cytoplasmic elements present in eukaryotic cells, and are involved in converting energy to ATP through oxidative phosphorylation. Mitochondria are vulnerable to reactive oxygen species (ROS), thereby making it imperative to evaluate the toxicity. However, existing methods that evaluate mitochondrial toxicity in cardiomyocytes are limited. Read More

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Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma.

J Oncol Pharm Pract 2022 May 23:10781552221102883. Epub 2022 May 23.

Division of Oncology, Department of Pediatrics, 6567Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Introduction: Memantine is used for neurocognitive protection in patients undergoing cranial radiotherapy for central nervous system tumors and is reported to be well-tolerated.

Case Report: Presented is a case of memantine-induced altered mental status requiring an intensive care unit admission. An 18-year-old male with relapsed, progressive medulloblastoma presented with severe altered mental status shortly after the first fraction of palliative whole brain radiotherapy. Read More

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Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure.

Authors:
Kazuhiko Sawada

Int J Mol Sci 2022 Apr 28;23(9). Epub 2022 Apr 28.

Department of Nutrition, Faculty of Medical and Health Sciences, Tsukuba International University, Tsuchiura 300-0051, Ibaraki, Japan.

The present study evaluated the neurogenesis of neonatal valproic acid (VPA) exposure on subventricular zone progenitors of the developing cerebral cortex in ferrets. VPA was injected at a dose of 200 µg/g of body weight into ferret infants on postnatal days 6 and 7. Two different thymidine analogues, 5-ethynyl-2'-deoxyuridine (EdU) and 5-bromo-2'-deoxyuridine (BrdU), were injected with a 48 h interval to label proliferating cells before and after VPA exposure. Read More

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Syringic acid and silymarin concurrent administration inhibits sodium valproate-induced liver injury in rats.

Environ Toxicol 2022 May 11. Epub 2022 May 11.

Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India.

Sodium valproate (SV) is a well-known anti-epileptic drug, also used to control convulsions, bipolar disorders and migraines. SV has been shown to induce liver toxicity in clinical subjects. Syringic acid (SA), a natural polyphenolic compound has potential antioxidant, anti-inflammatory and several beneficial effects. Read More

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Differentiation of PC12 cell line into neuron by Valproic acid encapsulated in the stabilized core-shell liposome-chitosan Nano carriers.

Int J Biol Macromol 2022 Jun 7;210:252-260. Epub 2022 May 7.

Nanobiotechnology Department, Faculty of Bioscience, Tarbiat Modares University, Tehran, Iran; Biophysics Department, Faculty of Bioscience, Tarbiat Modares University, Tehran, Iran. Electronic address:

Valproic acid (VPA) usage in high dose is teratogen with low bioavailability. Hence to improve its efficacy and reduce its side effect it was encapsulated by the Nano liposomes and stabilized by the chitosan at different concentrations. The cellular uptake, biocompatibility, loading and encapsulation efficiency of the six-different formulations (1:1, 2:1, and 4:1 of chitosan-phospholipids: VPA), PC12 differentiation to neuron cells assays (gene-expression level by qRT-PCR) were conducted for the efficacy assessment of the Nano carriers. Read More

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Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues.

Birth Defects Res 2022 May 9. Epub 2022 May 9.

National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.

Background: The developmental toxicity potential (dTP) concentration from the devTOX quickPredict (devTOX ) assay, a metabolomics-based human induced pluripotent stem cell assay, predicts a chemical's developmental toxicity potency. Here, in vitro to in vivo extrapolation (IVIVE) approaches were applied to address whether the devTOX assay could quantitatively predict in vivo developmental toxicity lowest effect levels (LELs) for the prototypical teratogen valproic acid (VPA) and a group of structural analogues.

Methods: VPA and a series of structural analogues were tested with the devTOX assay to determine dTP concentration and we estimated the equivalent administered doses (EADs) that would lead to plasma concentrations equivalent to the in vitro dTP concentrations. Read More

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Hitting Multiple Cellular Targets in Triple-Negative Breast Cancer Using Dual-Action Cisplatin(IV) Prodrugs for Safer Synergistic Chemotherapy.

ACS Biomater Sci Eng 2022 Jun 6;8(6):2349-2362. Epub 2022 May 6.

Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Sector 67, Mohali 160062, Punjab, India.

Triple-negative breast cancer (TNBC) cells show improved sensitivity for cisplatin therapy due to their defective DNA damage repair system. However, the clinical utilization of cisplatin is limited by dose-dependent systemic toxicities and chemoresistance. Cisplatin Pt(IV) derivatives having kinetically inert octahedral geometry provide an effective strategy to overcome these limitations. Read More

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A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness.

Neuro Endocrinol Lett 2021 Nov;42(7):464-483

Di Bella Foundation, Via Marconi 51, Post code 40122, Bologna, Italy.

Despite all the new developments in cancer therapy, the life expectancy of patients with malignant anaplastic brain tumors and glioblastoma multiform (GBM) remains short. Since the establishment of the Di Bella Method (DBM) in cancer therapy, DBM was able to increase the survival rate and life quality, without overt toxicity, in comparison to what is described in the literature related to the analogous brain tumors, with the same immunohistochemical, histologic and clinical features. Therefore, we treated seven patients with malignant anaplastic brain tumors using the DBM protocol. Read More

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November 2021

The Roles of Antidotes in Emergency Situations.

Emerg Med Clin North Am 2022 May 5;40(2):381-394. Epub 2022 Apr 5.

Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, 1391 Speer Boulevard, Suite 600, Denver, CO 80204, USA. Electronic address:

Management of the acutely poisoned patient requires supportive care and timely administration of antidotes to minimize ongoing toxicity and mortality. New applications for old antidotes include utilization of methylene blue and hydroxocobalamin in vasoplegia. Fomepizole is also being evaluated as a potential adjunct in acetaminophen toxicity. Read More

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Evaluation of the hepatoprotective activity of hydroalcoholic extract of Alhagi camelorum against valproic acid-induced hepatotoxicity in rats.

Biomed Pharmacother 2022 Jun 14;150:112953. Epub 2022 Apr 14.

Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan; Bakhtawar Amin College of Pharmaceutical Sciences, Multan, Pakistan. Electronic address:

Background And Purpose: Despite many liver disorders, clinically useful drugs are scarce. Moreover, the available therapies are facing the challenges of efficacy and safety. Alhagi camelorum has been used in folk medicine globally for millennia to treat several ailments. Read More

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Pseudo-Pelger-Huët neutrophil morphology due to sodium valproate toxicity.

Am J Hematol 2022 Apr 16. Epub 2022 Apr 16.

Faculty of Medicine, Centre for Haematology, St Mary's Hospital Campus of Imperial College, London, UK.

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Optimization of a locomotion-based zebrafish seizure model.

J Neurosci Methods 2022 Jun 11;375:109594. Epub 2022 Apr 11.

Department of Biology, KU Leuven, Naamsestraat 59, 3000 Leuven, Belgium. Electronic address:

Background: Locomotor assays in zebrafish have emerged as a screening test in early drug discovery for antiseizure compounds. However, parameters differ considerably between published studies, which may explain some discrepant results with (candidate) antiseizure medications.

New Method: We optimized a locomotor-based seizure assay in zebrafish with pentylenetetrazol (PTZ) as the pharmacological proconvulsant to generate a therapeutic window in which proconvulsant-treated zebrafish larvae could be discriminated from a non-treated control. Read More

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Effects of naringin and valproate interaction on liver steatosis and dyslipidaemia parameters in male C57BL6 mice.

Arh Hig Rada Toksikol 2022 Apr 7;73(1):71-82. Epub 2022 Apr 7.

University of Zagreb Faculty of Food Technology and Biotechnology, Zagreb, Croatia.

Valproate is a common antiepileptic drug whose adverse effects include liver steatosis and dyslipidaemia. The aim of our study was to see how natural flavonoid antioxidant naringin would interact with valproate and attenuate these adverse effects. For this reason we treated male C57BL6 mice with a combination of 150 mg/kg of valproate and 25 mg/kg naringin every day for 10 days and compared their serum triglycerides, cholesterol, LDL, HDL, VLDL, and liver PPAR-alpha, PGC-1 alpha, ACOX1, Nrf2, SOD, CAT, GSH, and histological signs of steatosis. Read More

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Comparison of four valproic acid free fraction determination methods used in clinical practice.

Farm Hosp 2022 02 14;46(2):80-83. Epub 2022 Feb 14.

Pharmacy Department, Hospital Universitario Severo Ochoa, Leganés (Madrid). Spain..

Objective: Given that hypoalbuminemia tends to result in higher free fraction  concentrations of valproic acid, different methods have been developed to  determine the latter in patients with this condition. The aim of this study is to  assess the reliability of these methods and, if necessary, design a new  estimation method.

Method: A retrospective analysis was carried out by the Pharmacy Department of Severo Ochoa University Hospital of admitted patients with at least one  trough concentration of valproic acid between October 2017 and February  2019. Read More

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February 2022

Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy.

Mol Biol Rep 2022 Mar 29. Epub 2022 Mar 29.

Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, 25240, Erzurum, Turkey.

Background: The present study investigated the effects of rutin (RUT), which has various biological and pharmacological properties, on liver and kidney damage caused by histone deacetylase inhibitor valproic acid (VPA), which is used in the treatment of many psychiatric disorders.

Methods And Results: In the study, 50 or 100 mg/kg RUT treatment was administered 30 min after 500 mg/kg VPA was given to rats for 14 days. Then, some pathways that may be involved in the damage mechanism of VPA in liver and kidney tissues were investigated using biochemical, RT-PCR and Western blotting techniques. Read More

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Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats.

BMC Complement Med Ther 2022 Mar 21;22(1):81. Epub 2022 Mar 21.

Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background: Convulsive status epilepticus (CSE) prevention is critical for pediatric patients with epilepsy. Immediate intervention before CSE reduce severity. Despite its wide usage as an anticonvulsant, valproic acid (VPA) results in harmful side effects such as dose-dependent hepatotoxicity. Read More

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A novel human stem cell-based biomarker assay for in vitro assessment of developmental toxicity.

Birth Defects Res 2022 Mar 14. Epub 2022 Mar 14.

Toxys B.V., Leiden Bio Science Park, Oegstgeest, The Netherlands.

Background: Testing for developmental toxicity according to the current regulatory guidelines requires large numbers of animals, making these tests very resource intensive, time-consuming, and ethically debatable. Over the past decades, several alternative in vitro assays have been developed, but these often suffered from low predictability and the inability to provide a mechanistic understanding of developmental toxicity.

Methods: To identify embryotoxic compounds, we developed a human induced pluripotent stem cells (hiPSCs)-based biomarker assay. Read More

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Valproic Acid Serum Concentration and Incidence of Toxicity in Pediatric Patients.

J Child Neurol 2022 May 7;37(6):461-470. Epub 2022 Mar 7.

Department of Pharmacy, 2468Rush University Medical Center, Chicago, IL, USA.

In certain pediatric patients on valproic acid, therapeutic range (50-100 μg/mL) is maximized or exceeded to achieve better seizure control. This study compared incidence of common valproic acid adverse effects (thrombocytopenia, hepatotoxicity, and hyperammonemia) across maintenance concentration and age group. One hundred twenty-four children on maintenance valproic acid between January 2013 and January 2021 were eligible for inclusion. Read More

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Management and Associated Toxicokinetics of Massive Valproic Acid Ingestion with High Flow Continuous Venovenous Hemodiafiltration.

J Med Toxicol 2022 07 2;18(3):239-242. Epub 2022 Mar 2.

Children's Hospital Colorado Anschutz Medical Campus, Aurora, CO, USA.

Introduction: Valproic acid (VPA) toxicity commonly results in a self-limited state of CNS depression that is managed with supportive care and levocarnitine. In massive overdose, patients can develop toxic encephalopathy, shock, multisystem organ failure, and death. We present a case with relevant toxicokinetics of a patient presenting with a profoundly elevated VPA concentration resulting in survival, treated with supportive care including high-dose continuous venovenous hemodiafiltration (CVVHDF). Read More

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Vitamin E rescues valproic acid-induced testicular injury in rats: Role of autophagy.

Life Sci 2022 May 25;296:120434. Epub 2022 Feb 25.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Egypt. Electronic address:

Aims: Valproic acid (VPA), a commonly used antiepileptic drug, can induce testicular oxidative stress and injury. Altered autophagic response usually follows testicular injury. The study aims to evaluate the role of autophagy in the protective effect of the antioxidant vitamin E (Vit E) against VPA-induced testicular injury. Read More

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An aqueous extract of Lantana camara attenuates seizures, memory impairment, and anxiety in kainate-treated mice: Evidence of GABA level, oxidative stress, immune and neuronal loss modulation.

Epilepsy Behav 2022 04 19;129:108611. Epub 2022 Feb 19.

Department of Psychology, University of Yaoundé I, P.O. Box 755, Yaoundé, Cameroon.

Background: Epilepsy is a neurological disorder characterized by spontaneous recurrent seizures. Lantana camara (Verbenaceae) is a plant used in Cameroonian traditional medicine to treat dementia, epilepsy, and sleeping disorders. Hence, this study aimed to assess the antiepileptic-like effects of an aqueous extract of L. Read More

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