2,672 results match your criteria: "Toxicity Valproate"

Introduction: In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints.

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Unraveling Copper Imbalance in Autism Spectrum Disorder: Mechanistic Insights from the Valproic Acid Mouse Model.

ACS Chem Neurosci

December 2024

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Abnormal copper (Cu) levels are often closely associated with neurological disorders including neurodevelopmental conditions, such as autism spectrum disorder (ASD). However, the mechanisms underlying the disruption of Cu homeostasis in critical organs, such as the brain, remain unclear. In this study, we elucidated the molecular mechanisms of Cu imbalance in the brain of a valproic acid (VPA) mouse model along with the changes in specific metabolites.

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The secretions of Telodeinopus canaliculatus, a giant millipede, are used in traditional medicine to treat epileptic seizures. Therefore, this work aimed to assess the antiepileptogenic- and anxiolytic-like effects of an extract of T. canaliculatu in mice.

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Preclinical liver toxicity models: Advantages, limitations and recommendations.

Toxicology

December 2024

Department of Pharmacology and Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai, India.

Experimental animal models are crucial for elucidating the pathophysiology of liver injuries and for assessing new hepatoprotective agents. Drugs and chemicals such as acetaminophen, isoniazid, valproic acid, ethanol, carbon tetrachloride (CCl), dimethylnitrosamine (DMN), and thioacetamide (TAA) are metabolized by the CYP2E1 enzyme, producing hepatotoxic metabolites that lead to both acute and chronic liver injuries. In experimental settings, acetaminophen (centrilobular necrosis), carbamazepine (centrilobular necrosis and inflammation), sodium valproate (necrosis, hydropic degeneration and mild inflammation), methotrexate (sinusoidal congestion and inflammation), and TAA (centrilobular necrosis and inflammation) are commonly used to induce various types of acute liver injuries.

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Article Synopsis
  • A 38-year-old woman experienced difficulty walking and focal seizures, showing signs of cerebellar dysfunction and spastic lower limbs, while having a long history of epilepsy treatment since the age of 20.
  • An MRI and MR spectroscopy indicated significant brain changes, including elevated lactate levels, suggesting a mitochondrial disorder.
  • Due to financial constraints preventing genetic testing, she was diagnosed with MELAS and switched to alternative treatments to manage her condition.
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Valproic acid (VPA) is a widely used antiepileptic drug, but its effects on oxidative stress in rodent models have not been systematically reviewed. This meta-analysis aimed to evaluate the impact of VPA on oxidative stress markers in rodents and explore underlying mechanisms through network pharmacology. A systematic search of PubMed, Web of Science, and PsycINFO (2010-2024) was conducted, following PRISMA and CAMARADES guidelines.

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  • Antiseizure medications, like valproic acid (VPA), show different results in patients due to genetic factors, though there's limited research specifically on VPA compared to other drugs.
  • This study aimed to analyze how genetic variations influence the effectiveness, side effects, and serum levels of VPA in patients with genetic generalized epilepsies (GGE).
  • The results revealed that certain genetic variants are linked to treatment failure, increased serum levels, weight gain, and hair loss among GGE patients using VPA, suggesting a need for personalized medication approaches.
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  • Sodium valproate is commonly used to treat seizures, chronic pain, and bipolar disorder, but it can cause severe side effects like valproate-induced hyperammonemic encephalopathy (VHE), which is life-threatening.
  • A study reviewed four neurosurgical patients who developed VHE after using valproate for seizure prevention, revealing a 50% mortality rate and indicating that prompt diagnosis and treatment are crucial.
  • Treatment involved discontinuing valproate and, in some cases, dialysis; half of the patients experienced clinical improvement after normalization of ammonia levels.
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  • - Type I Alexander disease is a severe neurological disorder that causes issues like seizures and developmental problems starting in early childhood, linked to a mutation in the GFAP gene.
  • - Although there's no cure, some treatments like ceftriaxone and amoxicillin have shown mild symptomatic improvement in patients by affecting glutamate levels in the brain.
  • - In a case study, a patient with severe irritability and seizures improved significantly after treatment with amoxicillin and perampanel, suggesting a potential role for glutamate-modulating drugs in treating this condition.
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  • - Toxigenic fungi can produce harmful substances known as mycotoxins, and identifying new or lesser-known types, called "emerging mycotoxins," is challenging due to silent genes.
  • - The study investigated the impact of four epigenetic modifiers (5-azacytidine, sodium butyrate, nicotinamide, and sodium valproate) on the metabolic profiles of a known toxigenic fungus, using advanced metabolomics techniques.
  • - Results showed that sodium valproate significantly increased the expression of dormant genes, resulting in the production of notable metabolites, particularly fusarins, which may have important implications for agriculture and food safety in areas affected by mycotoxins. *
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  • Mild traumatic brain injury (mTBI) is common, making up nearly 80% of all brain injuries, and it can cause neurological and cognitive issues even without visible damage.
  • Combining low doses of FDA-approved drugs lithium and valproate after a mild TBI has shown to improve learning and memory, recognizing that these benefits were not observed when either drug was used alone.
  • The treatment also reduced neuroinflammation, suggesting that this combination therapy might help mitigate damage and enhance cognitive function following mild brain injuries.
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  • - Valproate (VPA), commonly prescribed for epilepsy in children, can lead to liver issues like hepatic steatosis, but many cases may go unnoticed due to a lack of specific biomarkers.
  • - The study aimed to demonstrate that VPA causes triglyceride accumulation in liver cells and to identify microRNAs (miRNAs) linked to this effect as potential non-invasive biomarkers for liver steatosis in children.
  • - The researchers found that certain miRNAs were significantly altered in children taking VPA, and this signature identified 18 patients at risk for liver steatosis, highlighting a connection between high VPA levels, younger age, and liver enzyme changes.
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Cardiovascular developmental hazards of valproic acid in zebrafish.

Ecotoxicol Environ Saf

November 2024

Medical Research Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350013, China; Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian 350001, China. Electronic address:

Article Synopsis
  • * This study examined the effects of VPA on zebrafish embryos from 3 to 120 hours post-fertilization, finding time- and dose-dependent developmental delays, cardiovascular malformations, and impaired movement and reaction times.
  • * VPA exposure resulted in increased oxidative stress and cell death in heart cells, with altered gene expression linked to cardiovascular development and apoptosis, highlighting concerns about the risks of VPA exposure during early pregnancy.
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  • Valproic acid (VA) is commonly used for treating central nervous system disorders and is being explored for anticancer applications, but it has notable side effects.
  • Researchers studied a magnesium complex of valproate ([Mg(Valp)Phen]) and found it to be more cytotoxic than sodium valproate in both yeast and V79 cells.
  • The increased toxicity of the magnesium complex may be linked to its ability to cause DNA damage, requiring various DNA repair pathways to fix the lesions it induces.
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  • - The text discusses a rare case of anti-GABAB receptor autoimmune encephalitis (AE) in a 21-year-old male in Central America, where he presented with new onset seizures and status epilepticus after ruling out other potential causes.
  • - Diagnostic tests indicated lymphocytic pleocytosis in cerebrospinal fluid and positive anti-GABAB1-B2 receptor antibodies, leading to a confirmed diagnosis of AE despite initial normal imaging results.
  • - Treatment included corticosteroids, plasmapheresis, and immunoglobulin therapy, resulting in significant improvement; the patient has been seizure-free for seven months but is undergoing cognitive rehabilitation for mild cognitive decline.
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  • Recent advancements in HIV prevention highlight the effectiveness of pre- and post-exposure prophylaxis (PrEP and PEP), particularly in the context of new anti-seizure medications (ASMs) that have emerged since 2012.
  • The review discusses the potential drug interactions between PrEP/PEP and various ASMs, particularly focusing on enzyme-inducing ASMs that may lower the effectiveness of tenofovir-containing treatments, as well as the impact of ritonavir on lamotrigine levels.
  • Clinicians are encouraged to be aware of these interactions and side effects, such as osteopenia and gastrointestinal issues, to provide better care for patients who might be at risk for both seizures and HIV infection.
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  • - Dysfunction of the extraorbital lacrimal gland (ELG) can damage the cornea and lead to vision loss, prompting a study on the effects of sodium valproate (SV) and Moringa oleifera (M. oleifera) on rats.
  • - Results showed that SV treatment led to decreased antioxidant levels and increased oxidative stress, while M. oleifera extract treatment improved antioxidant status and reduced oxidative stress markers in rats also receiving SV.
  • - Protein analysis indicated that Moringa extract reversed some negative effects seen in SV-treated rats, highlighting its potential protective properties against oxidative damage related to SV use.
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  • Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a poor prognosis, leading researchers to explore the repurposing of existing drugs like valproic acid (VPA) and statins for potentially more effective treatments alongside standard chemotherapy.* -
  • The VESPA clinical trial is designed to investigate the combination of VPA and simvastatin (SIM) with gemcitabine/nab-paclitaxel in mPDAC patients, aiming to enhance treatment efficacy compared to chemotherapy alone.* -
  • The trial will enroll 240 patients across multiple centers, assessing outcomes like progression-free survival and overall survival, with a hypothesis that the combination therapy could extend progression-free survival from 6 to
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