Effect Of Sodium Valproate Research Articles

Anxiolytic and sedative effects of sodium valproate with different experimental paradigms in male and female rats.

Valproic acid or sodium valproate is a widely used drug in the treatment of epilepsy, although it also appears to have anxiolytic and sedative properties derived from its agonistic action on the GABAergic system. To analyze these potential effects of the drug, we conducted three experiments with rats using procedures designed to assess anxiety in rodents. In the first experiment, with a fear conditioning procedure, three groups of male rats were included that received either 100 mg/kg or 300 mg/kg of valproate or an equivalent volume of saline solution. In Experiment 2, recording spontaneous activity in an open field, we compared the effects of valproic acid (300 mg/kg) on male and female rats. In the third experiment, we analyzed the effect of valproic acid using a novelty-induced hypophagia test and tested again for potential differences as a function of the sex of the animals. The results showed an anxiolytic effect restricted to the 300 mg/kg dose of the drug in Experiment 1. Such an effect was restricted to the female sample in Experiment 2, but in the third experiment affected both sexes. As for the sedative effect, it was observed in all experiments irrespective of the sex of the rats. These findings hold significant implications for the treatment of anxiety disorders since valproate may offer a novel therapeutic approach for anxiety-related conditions with distinct benefits and fewer side effects. However, clinical studies are needed to validate the translation of these findings from animal models to human patients.

Sodium valproate affects the expression of p16INK4a and p21WAFI/Cip1 cyclin‑dependent kinase inhibitors in HeLa cells.

p16INK4a and p21WAF1/Cip1 are cyclin-dependent kinase inhibitors involved in cell cycle control, which can function as oncogenes or tumor suppressors, depending on the context of various extracellular and intracellular signals, and cell type. In human papillomavirus-induced cervical cancer, p16 INK4a shows oncogenic activity and functions as a diagnostic marker of cervical neoplasia, whereas p21 WAF1/Cip1 acts as a tumor suppressor and its downregulation is associated with the progression of malignant transformation. Several histone deacetylase (HDAC) inhibitors promote the positive and negative regulation of a number of genes, including p16 INK4a and p21 WAF1/Cip1; however, the effects of sodium valproate (VPA) on these genes and on the proteins they encode remain uncertain in HeLa cervical cancer cells. In the present study, these effects were investigated in HeLa cells treated with 0.5 or 2 mM VPA for 24 h, using reverse transcription-quantitative PCR, confocal microscopy and western blotting. The results revealed a decrease in the mRNA expression levels of p16 INK4a and a tendency for p16INK4a protein abundance to decrease in the presence of 2 mM VPA. By contrast, an increase in the protein expression levels of p21WAF1/Cip1 was detected in the presence of 0.5 and 2 mM VPA. Furthermore, VPA was confirmed to inhibit HDAC activity and induce global hyperacetylation of histone H3. Notably, VPA was shown to suppress p16 INK4a, a biomarker gene of cervical carcinoma, and to increase the abundance of the tumor suppressor protein p21WAF1/Cip1, thus contributing to the basic knowledge regarding the antitumorigenic potential of VPA. Exploration of epigenetic changes associated with the promoters of p16 INK4a and p21 WAF1/Cip1, such as histone H3 methylation, may provide further information and improve the understanding of these findings.

Evaluation of the effects of sodium valproate on plasma homocysteine, folate and vitamin B12 levels in epileptic patients

Evaluation of the effects of sodium valproate on plasma homocysteine, folate and vitamin B12 levels in epileptic patients

The Effect of Sodium Valproate as a Migraine Abortive: A Systematic Review and Network Meta-analysis (P6-12.002)

The Effect of Sodium Valproate as a Migraine Abortive: A Systematic Review and Network Meta-analysis (P6-12.002)

Analysis of the effect of sodium valproate on neuroimmune response in patients with refractory epilepsy

Analysis of the effect of sodium valproate on neuroimmune response in patients with refractory epilepsy

Sodium valproate with olanzapine in the treatment of mood disorder mania in construction project management

BackgroundWith increased social pressure and work intensity, construction workers face increasing mental pressure. In recent years, studies have shown that the incidence rate of mood disorder mania is gradually rising among construction workers in construction engineering. To ensure project progress and worker health, this study analyzed the effectiveness of sodium valproate combined with olanzapine in treating mood disorder mania in construction workers.Subjects and MethodsOne hundred construction workers diagnosed with mood disorder mania were randomly divided into an experimental and a control group, with 50 people in each group. The experimental group was treated with sodium valproate and olanzapine. The control group only used sodium valproate. The experiment lasted three months, and the patient’s status was evaluated using the Beck Ravensen Mania Scale (BRMS). Use Excel and SPSS24.0 to process the data statistically.ResultsAfter three months of treatment, the manic symptoms in the experimental group improved faster and had fewer side effects. The treatment effectiveness rate of the experimental group was as high as 86%, significantly higher than the control group’s 68%. Proved the effectiveness of sodium valproate combined with olanzapine treatment regimen.ConclusionsIn construction project management, sodium valproate combined with olanzapine can effectively alleviate symptoms and improve workers’ mental health and work efficiency for construction workers suffering from mood disorder mania.

Retracted: Analysis of the Clinical Effects of Sodium Valproate and Levetiracetam in the Treatment of Women with Epilepsy during Pregnancy.

[This retracts the article DOI: 10.1155/2021/5962200.].

Anti-hydatidosis Potential of Sodium Valproate: Evaluating New Therapeutic Potential for Sodium Valproate

Background: Larval stage of Echinococcus granulosus is the main cause of the hydatid cyst. Surgery, which is both aggressive and high-risk, is the most common treatment for this type of cyst. Some medicines, such as mebendazole, are also used as a complementary approach to preventing the recurrence of hydatid cysts. Objectives: Considering the approved antiparasitic effects of sodium valproate (VPA) on some parasites, this research intended to examine the potential of VPA against protoscolices and hydatid walls. Methods: Liver hydatid cysts caused by E. granulosus were collected from a slaughterhouse. Protoscolices and hydatid cysts were exposed to RPMI and dimethyl sulfoxide (DMSO) media (control groups) or different concentrations of VPA and mebendazole in vitro. The viability of protoscolices was evaluated via light microscopy. Also, tissue changes and expression of apoptotic caspase-3 were examined in hydatid cyst walls (HCWs) using histological and immunohistochemical methods, respectively. Results: The mortality rates of VPA-treated and mebendazole-treated protoscolices were dose- and time-dependent. There was a significant difference between the intervention and control groups (P < 0.05). Tissue changes and apoptosis were observed in VPA-treated and mebendazole-treated HCWs. Conclusions: Valproate and mebendazole had significant effects on protoscolices and HCWs, although VPA exerted its effects more rapidly. It seems that VPA can be a new promising protoscolicidal agent and anti-hydatid medicine.

Prognosticators of bone health in pediatrics with epilepsy using anti-epileptic drugs

Introduction: Epilepsy is a common and long-lasting neurological disorder in children who require long-term treatment with Antiepileptic drugs (AED). Such long-term AED use may have negative effects on bone causing bone loss and osteoporosis, necessitating frequent monitoring. Data on the effect of AED on bone health in children is scarce compared to adults and hence this study was undertaken. Aim: To compare and quantify the effects of sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) on bone health in children using specific bone biomarkers such as vitamin D, calcium, phosphorus, ALP, osteocalcin (OCN), and beta serum cross laps (CTx). Materials and methods: A prospective interventional study was carried out in Rajarajeswari Medical College and Hospital, Bangalore, between October 2019 to March 2022. A total of 79 confirmed cases of epilepsy within the age group of 1-18 years, receiving treatment with sodium valproate (SV), carbamazepine (CBZ), and levetiracetam (LEV) monotherapy for a period of minimum one month were enrolled. Serum samples of calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALP), Vitamin D were analyzed at the time of initiation of study and these levels were considered as baseline levels.

Low-Dose Digoxin is Associated with Anticonvulsant Effect Enhancement of Classical Antiepileptic Drugs in the Electro-Induced Seizures in Mice

The aim of the study was to determine the effect of low doses of cardiac glycoside digoxin on the anticonvulsant effect of five classical antiepileptic drugs, sodium valproate, topiramate, levetiracetam, clonazepam and phenobarbital, under experimental seizures in mice. Antiepileptic drugs were administered 30 min before to seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate – at doses of 300 and 150 mg/kg; levetiracetam – at doses of 100 and 50 mg/kg; phenobarbital – at doses of 20 and 10 mg/kg; clonazepam – at doses of 0.1 and 0.05 mg/kg body weight. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Maximal electroshock seizure model was reproduced by transmitting an electric current (strength – 50 mA, frequency – 50 Hz) through the corneal electrodes for 0.2 sec. It was found that low-dose digoxin potentiates the anticonvulsant effects of sodium valproate, topiramate and phenobarbital as well as modulates the effects of levetiracetam and clonazepam, showing a distinct pharmacological effect of their sub-effective doses and increasing their therapeutic potential even under incomplete seizure control – the equivalent of drug-resistant epilepsy. The obtained results substantiate the expediency of further study of digoxin as an anticonvulsant drug in the adjuvant therapy of epilepsy and other seizure conditions.

Evaluation of 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) as Potential Anticonvulsant Agent

It was determined that the studied 5-[(Z)-(4-nitrobenzylidene)]-2-(thiazol-2-ylimino)-4-thiazolidinone (Les-6222) affects the cyclooxygenase pathway of the arachidonic acid cascade, the markers of damage to neurons on models of PTZ kindling. In the model of chronic epileptogenesis in mice (pentylenetetrazole kindling), a 4-thiazolidinone derivative showed high anticonvulsant activity, which is weaker than the effect of sodium valproate and higher than Celecoxib. The mentioned compound has a pronounced anti-inflammatory effect in the brain on the background of the PTZ kindling, reliably inhibiting COX-1 and COX-2. The predominant inhibition of COX-2 by 44.5% indicates this enzyme’s high selectivity of Les-6222. According to the molecular docking study results, the studied compound revealed the properties of COX-1/COX-2 inhibitor and especially 5-LOX/FLAP. The decreasing content of 8-isoprostane in the brain of mice of the Les-6222 group indicates a beneficial effect on cell membranes in the background of oxidative stress during the long-term administration of PTZ. In addition, Les-6222 significantly decreased the content of neuron-specific enolase, indicating neuroprotective properties in the background of chronic epileptogenesis. The obtained results experimentally substantiate the feasibility of further developing Les-6222 as a promising anticonvulsant agent.

Effects of sodium valproate and levetiracetam monotherapy on vitamin D status in epileptic children: A study from Eastern India

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-α.

Methadone is the most frequently used opioid therapy worldwide, with controversial effects on oxidative stress homeostasis. This study investigated the effects of intraperitoneal (i.p.) co-administration of methadone (0.1, 0.3, 1, and 3 mg/kg) and valproate sodium (300 mg/kg) or gabapentin (50 mg/kg) in the mice maximal electroshock (MES)-induced seizure model. The adverse effect of drugs was assessed using the chimney test. The levels of tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) contents were measured in mice brains after a single seizure. Administration of methadone alone resulted in a significant reduction in the duration of hind limb extension (HLE) than that in the control group. Methadone pretreatment at doses of 0.1 and 0.3 mg/kg i.p. decreased, and at doses of 1 and 3 mg/kg i.p. had an increasing effect on anticonvulsant efficacy of gabapentin. Pretreatment with all doses of methadone significantly decreased the valproate anticonvulsive efficacy. At doses of 1 and 3 mg/kg i.p. methadone per se increased brain MDA levels after MES-induced seizure. Administration of methadone (0.3 mg/kg i.p.) enhanced and at 3 mg/kg decreased gabapentin effect on brain MDA level, but their co-treatment did not lead to further increase in MDA. Methadone at 0.3–3 mg/kg enhanced the effect of sodium valproate on MDA levels in the brain, but at all doses significantly potentiated its effect on brain TNF-α levels. The drugs did not produce any side effects on motor coordination in experimental animals. In conclusion, methadone showed different effects on anticonvulsant actions of gabapentin and valproate through regulation of brain levels of MDA and TNF-α.

Supercritical solvent impregnation of sodium valproate nanoparticles on polymers: Characterization and optimization of the operational parameters

To improve the bioavailability and reduce the therapeutic dose and side effects of Sodium valproate (S-VPA), nanoparticles of this drug were loaded on the polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) polymers via the supercritical solvent impregnation (SSI) process. This process was carried out at different pressures (150–250 bar), temperatures (308–328 K), and impregnation times (60–180 min). The Box–Behnken design (BBD) method was applied to study the effect of operational parameters on the S-VPA/PVP and S-VPA/HPMC loadings and optimize the condition. Maximum loadings on both PVP (1.56%) and HPMC (1.5%) were achieved at 250 bar, 318 K, and 180 min. Moreover, the impregnated samples (S-VPA/PVP and S-VPA/HPMC) were investigated by the FTIR, DSC, SEM, DLS, and XRD analysis. The S-VPA nanoparticles with the mean particle size of 27 nm and 128 nm were uniformly impregnated on the PVP and HPMC polymers, respectively. The results confirmed the lower crystallinity of the impregnated S-VPA nanoparticles, leading to their higher solubility and bioavailability. Finally, Enhanced S-VPA solubility was approved by comparing the dissolution rate of the original and the impregnated S-VPA samples in the optimum conditions.

Comparison of the Effects of Sodium Valproate and Carbamazepine on Renal Function in Children With Epilepsy

Background: Renal disorders have been observed with the long-term treatment of some antiepileptic drugs (AEDs). We aimed to compare the effects of carbamazepine (CBZ) and valproate (VPA) on renal function in children with epilepsy. Methods: This quasi-experimental study included children with epilepsy aged 2 months to 14 years who had persistently been receiving CBZ or VLP monotherapy for more than 6 months and were referred to Bandar Abbas Children’s Hospital, Bandar Abbas, Iran, 2019-2020. Demographic features, including age and sex, as well as family history of epilepsy, disease duration, and duration of treatment were recorded for each patient. Random blood and urine samples, along with 24-hour urine samples were collected from all the participants. Blood urea nitrogen (BUN), sodium, alkaline phosphatase (ALP), and pH were measured in blood samples. Glucose, protein, sodium, potassium, phosphorus, and creatinine were estimated in 24-hour urine samples. N-acetyl-beta-D-glucosaminidase (NAG) and pH were assessed in random urine samples. Results: Of the 80 children in this study with a mean age of 7.43±3.22 years, 58 (72.5%) were males. Children in both groups were comparable in terms of age, sex, family history of epilepsy, and disease and treatment duration. The urine NAG level was significantly higher in the VPA group compared to the CBZ group (P=0.010). Further, 24-hour urine protein and glucose levels were significantly higher in the VPA group. As for blood parameters, except for sodium (P=0.034), ALP (P<0.001), and pH (P=0.006) which were significantly higher in the CBZ group, other parameters were significantly higher in the VPA group. Conclusion: Overall, CBZ appears to be safer than VPA regarding its effects on renal function in children treated for epilepsy.

Effect of Sodium Valproate on Weight, Body Mass Index, Uric Acid, Vitamin D3, Blood Insulin, and Serum Lipid Profile in Children

Introduction: Due to the high prevalence of epilepsy and the use of sodium valproate as an antiepileptic drug by these patients, accurate recognition of its side effects and its effects on serum lipids profile, liver enzymes, uric acid level, and thyroid function tests, especially in cases that need long-term treatment seems essential. This study aimed to evaluate the effects of sodium valproate on weight, body mass index (BMI), vitamin D3, blood insulin, uric acid level, and serum lipids profile in children with newly diagnosed epilepsy. Materials and Methods: This prospective study was performed on 30 children between 3 and 8 years of age who suffered from newly diagnosed epilepsy and received sodium valproate as monotherapy. Data including demographic information (age, sex, height, weight, and waist and hip circumference of children), as well as clinical characteristics, such as liver enzymes (ALT, AST, ALK-P), serum lipids level (TG, TC, HDL-C, LDL-C), thyroid tests (TSH, T4), fasting blood sugar (FBS), uric acid level, 25 OH Vitamin D3 (Vit-D3), and blood insulin level of children before and six months after the consumption of sodium valproate, were examined. Results: The mean weight of children before and six months after the start of sodium valproate treatment was 18.54±2.99 and 21.13±3.93 (kg), respectively. This difference was statistically significant (P=0.005). Also, the mean weight Z-score of children before and after taking sodium valproate was -2.497 and -2.293, respectively, which was statistically significant too. In addition to weight gain, there was also a significant increase in the abdominal and hip circumference of children after taking valproate, whereas the increase in mean BMI before and after valproate administration was not statistically significant (P=0.114). However, mean weight gain, as well as the increase in the waist and hip circumference, had no relationship with gender (P> 0.05). Also, sodium valproate significantly increased the ALT level (P=0.046). Moreover, sodium valproate did not affect other liver function markers (AST), thyroid hormones (TSH, T4), fasting blood sugar (FBS), uric acid level, 25 OH Vit-D3, and the children's blood insulin levels (P> 0.05). Conclusion: According to the findings of this study, it can be concluded that sodium valproate is a good drug for children between 3 and 8 years of age, but it should be noted that taking this drug increases the chance of obesity in children. The main side effect of this drug is weight gain. Due to the significant increase in ALT enzyme, as observed in this study, it is recommended to check liver enzymes before, one, and six months after starting treatment as it can prevent the irreversible permanent side effects of this drug.

"The Effect of Sodium Valproate on Cardiovascular Responses in Pentylenetetrazol Kindling Model of Epilepsy"

"The Effect of Sodium Valproate on Cardiovascular Responses in Pentylenetetrazol Kindling Model of Epilepsy"

Valproic Acid Inhibits Glioma and Its Mechanisms.

Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate the effect of sodium valproate on the invasion and metastasis of glioma cells and its mechanism. Glioma cell lines were stimulated with VPA at different concentrations and for different durations of action. U87 glioma cells were transfected with Smad4 plasmid and small interfering RNA, and the changes of EMT-related protein indexes in U87 cells after up- or downregulation of Smad4 were detected by Western blotting. Immunohistochemistry was used to detect the differences in the expression of Smad4, TIF1-γ, and TGF-β proteins in 39 glioma clinical specimens from the Department of Pathology of our hospital. Based on the regulation of EMT-related transcription factors by VPA, our study indicates that VPA inhibits the EMT process of glioma by altering the expression level of Smad4, which is induced by TGF-β1 to form a Smad3/4 complex, thus inducing the EMT process of the tumor and acting as an antitumor target to inhibit the invasive ability of glioma cells. Sodium valproate inhibits glioma invasion and metastasis through the regulation of Smad4 expression.

The Effect of Valproate Sodium on the Electrical Activity of Helix aspersa F1 Neurons in a Pentylenetetrazole-Induced Epileptic Model Using an Intracellular Recording System

Background: Epilepsy is a chronic central nervous system disorder with a high prevalence in modern society. Despite using common anticonvulsant drugs, its control is not adequately achieved. Animal models for seizures play the leading role in advancing our understanding of the cellular mechanisms of epilepsy. The present study was an attempt to elucidate the electrophysiological mechanism of the effect of sodium valproate on the cellular model of epilepsy. Understanding the cellular mechanisms of this drug may help clarify the pharmacological screening of other drugs. Methods: The intracellular recording was made from F1 cells of garden Helix aspersa in the presence of Ringer solution. Following the extracellular application of valproate sodium at a concentration of 10 mM after and before the use of (25mM) epileptogenic agent (pentylenetetrazol (PTZ)), we evaluated its effect on paroxysmal depolarization shift (PDS) and electrophysiological characteristics. Results: These results showed that valproate sodium could reduce neuronal excitability. It could significantly hyperpolarize rest action potential by decreasing the frequency of firing rate and increasing the amplitude of afterhyperpolarization (AHP) and can prevent depolarization of rest action potential by PTZ. Conclusions: The results suggested that valproate sodium could reduce the PTZ-induced hyperexcitation by hyperpolarization of resting membrane potential (RMP), a reduction in AHP amplitude, and firing the frequency.

シスプラチン誘発急性腎障害に対するバルプロ酸ナトリウムの影響

シスプラチン誘発急性腎障害に対するバルプロ酸ナトリウムの影響