Side Effects Of Valproic Acid Research Articles

The Effect of Thyme Honey on the Histopathological Changes of the Testis in Relation to the Side Effects of Valproic Acid in Adult Male Wistar Rats

Introduction. Valproic acid (VPA) is a widely used drug in the treatment of emotional and nervous depression, mental imbalances, epilepsy, and control of bipolar disorders. Despite its therapeutic effects, VPA has toxic effects on male reproduction. The testis is an organ sensitive to oxidative stress. On the other hand, thyme honey contains antioxidant compounds. The aim of this study was to investigate the effect of thyme honey on the histopathological changes of the testis in relation to the side effects of VPA in adult male Wistar rats. Methods. In this study, 48 Wistar rats were used, which were randomly divided into equal eight groups and received their desired substances. Including the control group, Th1, Th2, and Th3 groups receiving 1, 2, and 3 g/kg of thyme honey, respectively, VPA (500 mg/kg), VPA + Th1 (500 mg/kg of VPA + 1 g/kg of thyme honey), VPA + Th2 (500 mg/kg of VPA + 2 g/kg of thyme honey), and VPA + Th3 (500 mg/kg of VPA + 3 g/kg of thyme honey). After 60 days, evaluation of malondialdehyde (MDA), total antioxidant capacity (TAC), and histological studies of hematoxylin-eosin and Masson’s trichrome staining were performed. Results. The use of thyme honey significantly improved some parameters related to spermatogenesis, and in addition, it increased sperm production in the honey groups. In addition, the changes in MDA levels in the groups have shown a decrease in the amount of lipid peroxidation in the VPA + Th2 group. The amount of TAC also increased after increasing the dose of thyme honey. Conclusion. Based on the results of this study, it seems that thyme honey has been able to reduce the side effects of VPA to some extent due to its high percentage of antioxidants.

The prevalence and risk factors of coagulopathy in pediatric patients undergoing surgery for epilepsy.

Hematological consequences of novel antiseizure medications (ASMs) or combined therapies are rarely reported, especially in pediatric patients undergoing surgery for epilepsy. This study aimed to assess the prevalence and risk factors of coagulation dysfunction in this population and evaluate their relationship with intra- and postoperative bleeding. Three hundred ninety children who underwent surgery for epilepsy and 104 children without epilepsy who underwent nonepilepsy surgery at the authors' center were included in the study. The authors retrospectively collected and analyzed the following clinical data: sex, age, weight, course of epilepsy, antiseizure therapy, first laboratory data after admission, and transfusion-related data. ASMs were responsible for the higher incidence of coagulation dysfunction in pediatric epilepsy surgery patients. Low body weight (OR 0.95, 95% CI 0.92-0.98) and valproic acid (VPA) therapy (OR 5.13, 95% CI 3.25-8.22) were the most relevant factors leading to coagulation dysfunction. The most common hematological side effects of VPA were thrombocytopenia and hypofibrinogenemia, whereas low body weight was only associated with hypofibrinogenemia. Both VPA and low body weight increased the need for intra- or postoperative transfusion (p < 0.001). Pediatric epilepsy surgery patients often take multiple ASMs, resulting in an increased incidence of coagulopathy. VPA levels and low body weight were found to be the main influential factors associated with an increased risk of coagulation dysfunction. Platelet and fibrinogen levels were the main indices that were affected. Both VPA and low body weight were relevant to additional surgery-related transfusion, necessitating the need for increased awareness of preoperative coagulopathy before pediatric epilepsy surgery. Clinical trial registration no.: NCT05675254 (ClinicalTrials.gov).

Mitochondrial Toxic Effects of Antiepileptic Drug Valproic Acid on Mouse Kidney Stem Cells.

Valproic acid (VPA) is a histone deacetylase inhibitor that is used mainly as an antiepileptic and anticonvulsant drug. The side effects of VPA usually appears as hepatic injury and various metabolic disorders. On the other hand, it is rarely reported to cause kidney injury. Despite the many studies on the influence of VPA exposure on the kidneys, the specific mechanism remains unclear. This study examined the changes after VPA treatment to the mouse kidney stem cells (mKSCs). VPA triggers an increase in mitochondrial ROS, but there was no change in either mitochondrial membrane potential or the mitochondrial DNA copy number in mKSCs. The VPA treatment increased the mitochondrial complex III but decreased complex V significantly compared to the DMSO treatment as a control. The inflammatory marker (IL-6) and the expression of the apoptosis markers (Caspase 3) and were increased by VPA. In particular, the expression of the podocyte injury markers (CD2AP) was increased significantly. In conclusion, VPA exposure has adverse effects on mouse kidney stem cells.

Side effects of valproic acid: daytime incontinence and nocturnal enuresis

Side effects of valproic acid: daytime incontinence and nocturnal enuresis

Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid.

Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA. Charts of adult patients with SE from St. Mary's Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic. There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P<0.001). Hyperammonemia was identified in 32 and associated with younger age, being in a non-neurological intensive care unit, and liver disease, but was not statistically associated with VPA. Only one patient had valproate-induced hyperammonemic encephalopathy; however, many patients received treatment for hyperammonemia such as lactulose, levocarnitine, or VPA dose reductions. This study demonstrated variability in ammonia testing and management changes in SE but does not support the routine monitoring of ammonia levels and showed that hyperammonemic encephalopathy was rare in this clinical setting.

Hematological changes in adult patients on valproic acid therapy

Introduction: Valproic acid (VPA) is one of the commonly used anti-epileptic drugs. It is also an effective mood stabilizing drug. Despite its therapeutic benefits, hematological toxicity of valproic acid is increasingly encountered. Therefore, this study was carried out to evaluate the various hematological changes in adult patients on VPA and to closely monitor them so as to prevent the life threatening side effects of VPA. Aims and Objectives: (1) To study the spectrum of hematological changes in adult patients on VPA therapy and its distribution in different age groups and sex. (2) To establish a correlation between the dosage and duration of VPA therapy and its hematological effects.Materials and Methods: The present study was a prospective study done over a period of one year. A total of 50 adult patients on VPA therapy for atleast six months duration and attending the out -patient department (OPD) in General hospitals under the Bangalore rural district were included in the study. Results: A total of 50 adult patients on VPA therapy were included in the study. The patients were categorized into different age groups and sex. Female to male ratio was 2.6:1. Females constituted 72% of the total number of cases. The majority of the patients were in the age group of 26-35 years constituting 36% of the total number of cases. The spectrum of hematological changes were isolated anemia (8%), isolated leucopenia (4%), isolated thrombocytopenia (28%), bicytopenia (28%) and pancytopenia (24%). A direct correlation was established between the dosage as well as the duration of VPA therapy and the hematological changes observed especially in the elderly females. A significant negative correlation was found between the dosage of VPA therapy and the platelet and leucocyte counts.Conclusion: The study helps in identifying the potential risk factors, closely monitoring the patients on VPA and preventing life-threatening side effects. It also helps the clinicians in dose adjustments and sensitizes them to be cautious while prescribing VPA in higher doses and for longer duration.

Effect of Valproic Acid on Retina

Anti-epileptic drugs (AEDs) are the main form of treatment for people with epilepsy. Around 70% epileptic patients may have their seizures controlled by taking these medications. Valproic acid is one of the most common drugs using for epileptic patients. This drug has some side effects like nausea, vomiting, bleeding, abdominal cramps, diarrhea, headache. In this research, we want to study on possible side effects of Valproic acid on eye in patients with epilepsy. Methods and Materials: In this study, we had 28 patients suffering from epilepsy and seizures who take Valproic acid for at least two years. The control group was included of 28 subjects with no history of taking this drug and no visual problem. Electroretinogram (ERG) obtained were compared with both groups to find possible changes. Results: The mean voltage of ERG was 92.98 ± 12.67 and 92.16 ± 13.47 μV in case and control groups, (P>0.05). The mean latency was 43.2 ± 3.06 and 44.80 ± 4.36 msec in case and control groups, with P>0.05. These findings show that there is no Significant difference in ERG parameters in case and control groups. Conclusions: By the result of this research, it can be concluded that Valproic acid does not have any side effects on the retina in patients taking this drug.

The Investigation of Insulin Resistance in Two Groups of Epileptic Patients Treated with Sodium Valproate and Carbamazepine.

Background:Valproic acid (VPA) is a widely used broad-spectrum antiepileptic drug for therapy of generalized and focal epilepsies. Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia. We decided to investigate hyperinsulinemia as a health-threatening side effect of VPA in Iranian epileptic patients.Materials and Methods:Body mass index (BMI), lipid profile, fasting serum insulin, fasting blood glucose (FBS), and homeostatic model assessment-insulin resistance (HOMA-IR) were measured in 30 VPA-treated epileptic patients and 30 controls (CBZ-treated). The Chi-square test, t-test, and Pearson correlation test were used.Results:BMI was higher in VPA group than in control group (25.7 ± 3.5 > 21.7 ± 4.1) (0.000 < 0.05). Prevalence of obesity was 16.6% in VPA group that was almost the same and even lower than general Iranian population. Serum triglyceride (TG) (150 ± 77.2) was higher than CBZ group (114 ± 35.2) (P = 0.023 < 0.05). However, serum high-density lipoprotein level was lower in VPA group than controls (45.2 ± 11.7 < 54.4 ± 13.9) (P = 0.008 < 0.05). Serum insulin, FBS, HOMA-IR, cholesterol, and low-density lipoprotein did not demonstrate statistically significant differences between the two groups (P > 0.05).Conclusion:Despite the majority of previous studies that are against VPA and according to our study, VPA could be prescribed safely and it may not cause IR and its complications.

My epilepsy story: What is it like to be absent?-A message from an "ex"-patient.

My epilepsy story: What is it like to be absent?-A message from an "ex"-patient.

Effects of long-term valproic acid treatment on hematological and biochemical parameters in adolescent psychiatric inpatients: a retrospective naturalistic study.

The objective of this study was to determine the long-term hematological and biochemical side effects of valproic acid (VPA) in psychiatric adolescent inpatients. A retrospective naturalistic study design was used. Participants were psychiatric inpatients treated with VPA, alone or in combination with other medications. Electronic medical files were reviewed for changes in hematological and biochemical parameters following a course of VPA treatment. One hundred and four adolescents aged 12-18 (mean 15.76±1.58) years fulfilled the study criteria. The mean blood level and duration of VPA treatment were 65.81±22.18 mcg/ml and 98.57±135.94 days, respectively. The mean levels of thyroid-stimulating hormones and triglyceride levels increased significantly from the first to the last measurement. Platelet count decreased significantly following VPA treatment. No correlation was observed between these parameters and age, duration of treatment, or VPA levels. No serious adverse events were reported. Long-term VPA treatment in adolescents with psychiatric disorders is associated with significant increases in triglyceride levels. Moreover, VPA-treated adolescent psychiatric inpatients may be at risk of developing pituitary-thyroid axis dysregulation and decreased platelet count. Therefore, baseline measurement of thyroid functions and metabolic and hematological parameters and monitoring throughout the treatment are recommended.

Valproic acid and nonalcoholic fatty liver disease: A possible association?

Valproic acid (VPA) is one of the most prescribed drugs in children with newly diagnosed epilepsy. Weight gain and obesity have been observed as side effects of VPA. These are often linked with other metabolic disturbances such as development of insulin resistance, dyslipidemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD). NAFLD refers to a group of liver disorders with marked hepatic steatosis. It is associated with an increased incidence of cardiovascular diseases and overall reduced life expectancy. NAFLD occurs in 20%-25% of the general population and it is known to be the most common cause of chronic liver disease. NAFLD therefore represents a major public health issue worldwide. This study reviews and summarizes relevant literature that supports the existence of an association between VPA therapy and the development of NAFLD in children. Long-term VPA-therapy appears to be associated with an increased risk of developing NAFLD. Further studies are needed to clarify the pathogenic mechanisms that lie behind this association and to standardize the options for the use of this drug in overweight patients and in those with risks for developing MetS and NAFLD.

Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid.

Valproic acid (VPA) is ubiquitously used as a major drug in the intervention of epilepsy and in the control of several kinds of seizures. Cellular toxicities are the serious dose-limiting side effects of VPA when applied in the treatment of diseases. Oxidative stress has been proven to be involved in VPA-induced toxicity. Accumulating evidence intimates that oxidative stress caused by free radicals and in kidney cells contributes to the pathogenesis of VPA-induced nephrotoxicity. The pathogenesis of these forms of VPA nephrotoxicity is still not clear. The aim of our investigation was to evaluate the nephrotoxic potential of VPA and protective effects of quercetin (QR) against VPA-induced nephrotoxicity by using rat kidney tissue preparation as an in vitro model. Oxidative stress indexes such as lipid peroxidation (LPO) and protein carbonyl (PC) content were appraised. The levels of oxidative stress markers, LPO, and PC were significantly elevated. Nonenzymatic antioxidants effect was also demonstrated as a significant increase in reduced glutathione (GSH) and nonprotein thiol level (NP-SH). VPA exposure altered the activities of glutathione metabolizing enzymes such as glutathione-S-transferase, glutathione peroxidase, and glutathione reductase. Pre-treatment with QR could reverse the VPA-induced effects in kidney tissue preparation of rat. Based on reno-protective and antioxidant action of QR, we suggest that this flavonoid compound could be considered as a potential safe and effective approach in attenuating the adverse effect of VPA-induced nephrotoxicity.

Primum non nocere: A case of valproate encephalopathy

Summary Valproic acid (VPA) is a traditional antiepileptic which is used in the treatment of some types of epileptic seizures. Encephalopathy is a side effect of VPA which leads to rare but serious results and hyperammoniemia may be accompanied by one of these statements. It is specified that asymptomatic hyperammoniemia which VPA revealed is 20% and the incidence of symptomatic hyperammoniemia is 5%. The reason why VPA induced hyperammoniemia pathogenesis is not fully understood. In this article we present a 60-year-old male patient who was diagnosed VPA induced encephalopathy. The case presented is the first in the literature, in that, the patient previously taking valproate and whose encephalopathy unmonitored, valproate has been used after repeated seizures; and, after that encephalopathy has emerged.

Chronic exposure to valproic acid promotes insulin release, reduces KATP channel current and does not affect Ca2+ signaling in mouse islets

Hyperinsulinemia is one of the reported side effects of valproic acid (VPA), a medicine used to treat epilepsy. However, its underlying mechanism remains unknown. The present study was designed to investigate a direct effect of VPA on insulin secretion by using mouse pancreactic islets and β-cells. VPA had no acute effect on insulin secretion from islets, or on cytosolic Ca(2+) ([Ca(2+)]i) in single β-cells. However, following long-term exposure to VPA (48h), both basal and glucose-stimulated insulin secretion were markedly elevated (5-fold), while the insulin gene expression level was unaltered. Following long-term exposure to VPA, β-cells showed a decrease in whole cell KATP channel current. However, the increase in [Ca(2+)]i in response to the sulfonylurea drug, tolbutamide was attenuated. The present study shows that VPA has no acute effects, but long-term treatment results in enhancement of both basal and glucose-stimulated insulin secretion. This long-term effect may mediate the KATP channel, while VPA can also attenuate the effect of the KATP channel blocker tolbutamide.

DGI-079 Valproic Acid and Behaviour Disorders: Observation of Efficiency and Toxicity in a Cognitive-Behavioral Unit

BackgroundIn order to limit neuroleptic use in the elderly, because of cardiovascular events, specialists in charge of behaviour disorders don’t have many therapeutic options in cognitive-behavioural units (CBU).Purpose Valproic acid...

A Case of Valproate Induced Hyperammonemic Encephalopathy in an Elderly Bipolar Patient Under Treatment With Sulphonylureas

Valproic acid induced hyperammonaemic encephalopathy (VPA-VHE) is a rare side effect of valproic acid. It is characterized by impaired consciousness and lethargy, focal neurological signs or symptoms with a serum level of ammonia above 40 mmol/L. This syndrome is often misdiagnosed, especially in psychiatricsetting.Wepresentthe case of a bipolar patient who developed VPA-VHE. He assumed also sulphonylureas to manage mild hyperglycemia. After three months of treatment with valproic acid patient had a depressive episode and acute onset of headache, disorientation, consciousness impairment, and psychomotor slowing. This presentation induced to make investigation and we have discovered hyperammonaemia with EEG alteration; a diagnosis of valproate induced hyperammonemic encephalopathy (VHE) was made. The patient recovered quickly after discontinuing valproic acid therapy. Valproic acid is a frequent treatment in psychiatricsetting and a betterknowledge of possibleadverseeffectsisimportant to prevent and manage rare conditions like VHE. J Med Cases. 2013;4(8):540-543 doi : http://dx.doi.org/10.4021/jmc1313w

Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications

In the last years, a growing body of literature indicates an association between valproic acid therapy and weight gain. Weight gain during valproate treatment can be observed within the first 3 months of therapy and women seem to be more susceptible than men. The mechanism through which valproic acid may induce a weight gain is still controversial. The scope of this paper is to investigate the possible causal link between treatment and weight gain in epileptic patients. Systematic review of published epidemiological studies has been done in order to evaluate the real extent of this side effect of valproic acid and its clinical implications, such as an increased risk of insulin resistance and other secondary metabolic abnormalities. The knowledge of the potential of valproic acid to cause significant changes in body weight will help in appropriate selection and modification of antiepileptic therapy to minimize the risk for weight abnormalities. Measurements of body weight before initiation of valproic acid therapy should be done as part of the monitoring of patients with epilepsy to detect changes before there are serious adverse consequences; an increase of 2 kg of body weight after 1 month of treatment should imply considerations to change antiepileptic drug therapy.

202 Activation of breast cancer cell proliferation by ROR-alpha through aromatase promoter

<dm:abstracts xmlns:dm="http://www.elsevier.com/xml/dm/dtd"><ce:abstract xmlns:ce="http://www.elsevier.com/xml/common/dtd" id="abs0005" class="author-highlights" view="all"><ce:section-title id="sect0005">Highlights</ce:section-title><ce:abstract-sec id="abst0005" view="all"><ce:simple-para id="spar0005" view="all"><ce:list id="lis0005"><ce:list-item id="lsti0005"><ce:label>•</ce:label><ce:para id="par0005" view="all">A paradoxical phenomenon of hair growth by valproic acid is identified in studies.</ce:para></ce:list-item><ce:list-item id="lsti0010"><ce:label>•</ce:label><ce:para id="par0010" view="all">Valproic causes alopecia.</ce:para></ce:list-item><ce:list-item id="lsti0015"><ce:label>•</ce:label><ce:para id="par0015" view="all">Valproic acid also can cause hair growth.</ce:para></ce:list-item></ce:list></ce:simple-para></ce:abstract-sec></ce:abstract><ce:abstract xmlns:ce="http://www.elsevier.com/xml/common/dtd" id="abs0010" view="all" class="author"><ce:section-title id="sect0010">Abstract</ce:section-title><ce:abstract-sec id="abst0010" view="all"><ce:simple-para id="spar0010" view="all">Valproic acid is being used as the first line of treatment for multiple types of seizures disorders, also as a mood stabilizer in patients with bipolar affective disorder and also in other psychiatric disorders. Although having a well-being effect in above mention conditions valproic acid also cause significant side effects liketremor, weight gain, hair loss, and gastrointestinal disturbances, heartburn, liver dysfunction, and thrombocytopenia etc. Hair loss is the well-known side effect of valproic acid. Hair loss induced by valproate(anexample of telogen effluvium)is diffused, non-scarring and dose dependent. But recent studies also have shown that this valproic acid can also show paradoxical phenomenawhen it is administered topically i.e. “valproicacid-induced hair growth”. Here we are putting these both psychopharmacological aspects of the valproate together with emphasis on newly known paradoxical phenomena that can be utilized as a treatment option for valproate-induced alopecia.</ce:simple-para></ce:abstract-sec></ce:abstract></dm:abstracts>

203 Inhibin A is downregulated during chemotherapy in patients with breast cancer

<dm:abstracts xmlns:dm="http://www.elsevier.com/xml/dm/dtd"><ce:abstract xmlns:ce="http://www.elsevier.com/xml/common/dtd" id="abs0005" class="author-highlights" view="all"><ce:section-title id="sect0005">Highlights</ce:section-title><ce:abstract-sec id="abst0005" view="all"><ce:simple-para id="spar0005" view="all"><ce:list id="lis0005"><ce:list-item id="lsti0005"><ce:label>•</ce:label><ce:para id="par0005" view="all">A paradoxical phenomenon of hair growth by valproic acid is identified in studies.</ce:para></ce:list-item><ce:list-item id="lsti0010"><ce:label>•</ce:label><ce:para id="par0010" view="all">Valproic causes alopecia.</ce:para></ce:list-item><ce:list-item id="lsti0015"><ce:label>•</ce:label><ce:para id="par0015" view="all">Valproic acid also can cause hair growth.</ce:para></ce:list-item></ce:list></ce:simple-para></ce:abstract-sec></ce:abstract><ce:abstract xmlns:ce="http://www.elsevier.com/xml/common/dtd" id="abs0010" view="all" class="author"><ce:section-title id="sect0010">Abstract</ce:section-title><ce:abstract-sec id="abst0010" view="all"><ce:simple-para id="spar0010" view="all">Valproic acid is being used as the first line of treatment for multiple types of seizures disorders, also as a mood stabilizer in patients with bipolar affective disorder and also in other psychiatric disorders. Although having a well-being effect in above mention conditions valproic acid also cause significant side effects liketremor, weight gain, hair loss, and gastrointestinal disturbances, heartburn, liver dysfunction, and thrombocytopenia etc. Hair loss is the well-known side effect of valproic acid. Hair loss induced by valproate(anexample of telogen effluvium)is diffused, non-scarring and dose dependent. But recent studies also have shown that this valproic acid can also show paradoxical phenomenawhen it is administered topically i.e. “valproicacid-induced hair growth”. Here we are putting these both psychopharmacological aspects of the valproate together with emphasis on newly known paradoxical phenomena that can be utilized as a treatment option for valproate-induced alopecia.</ce:simple-para></ce:abstract-sec></ce:abstract></dm:abstracts>

Molecular and Therapeutic Potential and Toxicity of Valproic Acid

Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.