Valproic acid can reduce the frequency of seizures through various mechanisms and is widely used in clinical practice as a monotherapy or adjunctive treatment for various types of epilepsy and epileptic syndromes. In addition, valproic acid has significant therapeutic effects on comorbidities associated with epilepsy, such as migraines and psychiatric disorders. It can also be effective in terminating status epilepticus and is commonly used as a broad-spectrum antieseizure medication in clinical settings. However, valproic acid has side effects such as teratogenicity, infertility, and menstrual disorders. Additionally, when used in combination with other drugs, the interactions between medications should be carefully considered. Therefore, in clinical practice, it is necessary to strictly adhere to the indications and dosage regimens for the use of valproic acid. This article provides a comprehensive review of the use of valproic acid in different types of seizures, epileptic syndromes, comorbidities associated with epilepsy, post-craniotomy cases, status epilepticus, and special populations. It also summarizes the combination therapy of valproic acid with other drugs, providing a basis for the rational use of valproic acid and individualized drug treatment selection for epilepsy patients.
Objective To investigated the influence of the CYP2C9 polymorphism on lipid profile and blood concentration in epileptic children with VPA. Methods This study collected the information of healthy children and epilepsy children who were treated with VPA in the First Affiliated Hospital of Putian University during June, 2018 to March, 2021. The serum lipids of 184 cases were collected and compared between epilepsy group before and after treatment with VPA with the control group. The polymorphism of CYP2C9 gene in children with epilepsy was detected, and lipid and VPA concentration were compared after classification. Results There was no significant difference in lipid between the control group and the epilepsy group before treatment (P>0.05); The TC, HDL, LDL, TC/HDL, LDL/HDL were statistically different in VPA treatment group from the control group (P<0.05), and there were statistical differences in TG, LDL, TC/HDL, LDL/HDL between the trial group before the initiation and VPA treatment (P<0.05); There is no correlation between VPA blood concentration and lipid (P>0.05). VPA concentration, TC, HDL, LDL, TC/HDL and LDL/HDL in CYP2C9 wild-type were statistically different from heterozygous mutant. Conculsions CYP2C9 polymorphism and long-term use of VPA caused the changes in serum lipid levels in epilepsy children.
ObjectiveTo investigate the effect of valproic acid (VPA) coadministred with lamotrigine (LTG) on epileptic patients' ammonia and evaluate the influencing factors of elevated blood ammonia in epileptic patients.MethodsA retrospective analysis of clinical data from 146 patients with epilepsy (including newly diagnosed epilepsy patients) who were admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University from May 2018 to April 2020 was performed. The patients were divided into no antiepileptic drug group (group A), VPA group only (group B) and VPA combined LTG group (group C), and the concentration of the blood ammonia of the patients were analyzed.ResultThe average ammonia levels in groups A, B and C were (18.14±1.19), (25.89±0.87) and (36.60±4.34) μmol/L, and the incidence of blood ammonia higher than normal were 2.77%, 8.89% and 20.0%, respectively.The difference between group B and group A and group C were statistically significant (P<0.05), the difference between group C and group A was statistically significant (P<0.05).ConclusionPatients with epilepsy who use VPA were at increased risk of blood ammonia and LTG can increase ammonia in epileptic patients who were treated with VPA. So when VPA was combined with LTG, more attention should be paid to ammonia of patient to avoid adverse reactions.
Objective To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. Methods BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. Results The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. ConclusionVPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
ObjectiveTo explore the inhibition action of valproic acid to inflammatory cells and smooth muscle cells then to find out that valproic acid (VPA) can repress rat thoracic aortic aneurysm or not. MethodsThe model of rat thoracic aortic aneurysm was built through the method of soaking the adventitia of artery using porcine pancreatic elastase (PPE). The rats were divided into three groups:a normal saline blank control group (a C group), an adventitia soaked PPE group (a P group), and adventitia soaked PPE plus intraperitoneal injection by injecting intraperitioneal VPA 200 mg/kg for seven days (a PV group).The animals of the three groups were all using vascular ultrasound to detect blood vessel diameter. Animals were killed after operation to observe the general morphology of vascular aneuysm and do the immunohistochemial, morphological, protein analysis of interleukin 1 (IL-1), interleukin 6 (IL-6), smooth muscle 22 alpha (SM22α), matrix metallopeptidase 2 (MMP-2), MMP-9 and Western blot by drawing animals on the 14th day. ResultsThe vessels diameter in the PV group was narrower than that in the P group (P value<0.05). HE staining, immunohistochemistry and Western blot displayed that the cells in the P group were in disorder arrangement and interstitial disorder while the cells in the PV group maintained better albumin layer. The protein expressions of IL-1, IL-6, MMP-2, and MMP-9 in the PV group decreased except that SM22α increased. ConclusionVPA can inhibit phenothpic transforming of aneurysm inflammatory cells and smooth muscle cells, reduce the levels of cell proliferation, decrease the secretion of matrix metalloproteinases, and depress tumor growth of rat thoracic aorta.
ObjectiveTo compare the curative effect of levetiracetam combined with lamotrigine and sodium valproate on postoperative patients with temporal lobe epilepsy. MethodsA total of 186 postoperative patients with temporal lobe epilepsy during August 2012 to August 2014 in our hospital were divided into levetiracetam combined with lamotrigine group (n=98), and sodium valproate group (n=88) based on postoperative different antiepileptic drugs treatment. Antiepileptic treatment were followed up for 12~48 months.Curative effect and adverse reaction were observed. Reservation rates and incidence rates of adverse reaction were calculated in the two groups. ResultsIn levetiracetam combined with lamotrigine group, EngelⅠratio was 72.4%(71), EngelⅡratio was 17.3%(17), EngelⅢratio was 7.1%(7), and EngelⅣratio was 3.2%(3);in sodium valproate group, EngelⅠratio was 67.0%(59), EngelⅡratio was 21.6%(19), EngelⅢratio was 9.1%(8), and EngelⅣratio was 2.3%(2), and the difference was not statistically significant in the same grade of two groups (P > 0.05).Reservation rate and incidence rate of adverse reaction in levetiracetam combined with lamotrigine group were 90.8%(89) and 15.3%(15) respectively.While those in sodium valproate group were 80.7%(71) and 36.4%(32) respectively.The differences were statistically significant between the two groups (P < 0.05). ConclusionsLevetiracetam combined with lamotrigine treatment on postoperative patients with temporal lobe epilepsy may have better curative effects than sodium valproate treatment, and levetiracetam combined with lamotrigine has its advantage in reservation rate and less adverse reaction.