Background:To explore the antioxidant capacity ofα-asarone(ARE)in mice models of sodium valproate(SV)-induced liver injury,and to elucidate the underlying mechanism of ARE in liver injury treatment.Methods:Network ph...Background:To explore the antioxidant capacity ofα-asarone(ARE)in mice models of sodium valproate(SV)-induced liver injury,and to elucidate the underlying mechanism of ARE in liver injury treatment.Methods:Network pharmacology and molecular docking were used to predict ARE’s potential pharmacological mechanisms in treating drug-induced liver injury.AML12 cell model was used to evaluate the antioxidant stress activation of ARE.In the evaluation of antioxidant activity,ARE was tested for its ability to scavenge hydroxyl radical(OH)radicals,2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS+),and 1,1-diphenyl-2-picrylhydrazyl(DPPH),with vitamin C serving as the positive control.And thirty-six male mice were divided into six groups.Group I,the control,received saline.The other five groups received oral doses of 500 mg/kg/b.w.of SV daily for 14 days.Group II received only SV.Group III received the hepatic protectant bifendate at 100 mg/kg/b.w.,while groups IV,V,and VI were treated with 20,40,and 80 mg/kg/b.w.of ARE,respectively,also for 14 days.After sacrifice,liver and blood samples were collected for biochemical or metabolomic analysis.Results:ARE significantly reduced the levels of reactive oxygen species and activated the Keap1/Nrf2 signaling pathway in liver injury AML12 cells.ARE demonstrated dose-dependent scavenging activity in DPPH,ABTS+,and OH assays.It lowered serum alanine aminotransferase and aspartate aminotransferase levels,increased glutathione peroxidase and superoxide dismutase activity in liver tissue,and reduced malondialdehyde content.Metabolomic analysis showed that ARE restored twenty liver metabolites to control levels and enriched three pathways(arginine biosynthesis,sucrose and starch metabolism,and biotin metabolism)with shared differential metabolites.Conclusion:These results shed light on ARE’s mechanism in reducing oxidative stress,suggesting a potential strategy for preventing SV-induced liver disease by modulating metabolic products and enhancing antioxidant capacity.ARE could be a promising drug candidate for its antioxidant and liver-protective effects.展开更多
Objective:To explore the effect of black radish(Raphanus sativus L.var niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced hepatotoxicity.Method...Objective:To explore the effect of black radish(Raphanus sativus L.var niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced hepatotoxicity.Methods:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were assessed.Results:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological alterations.The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological changes.Conclusions:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.展开更多
The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges i...The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K ＋ concentration （8.5 mmol/L） in the bath, and the effects of the anti-epileptic drug valproate （VPA） on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration （100 μmol/L） suppressed the propagation speed but not the rate or duration of high-K＋-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.展开更多
BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming app...BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming apparent,particularly hepatotoxicity.Herein,we report a case of fatal acute liver failure(ALF)with thrombotic microangiopathy(TMA)caused by treatment with sodium valproate in a patient following surgery for meningioma.CASE SUMMARY A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue,severe jaundice accompanied by oliguria,soy sauce-colored urine,and ecchymosis.His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level,severe liver and kidney dysfunction,and disturbance of the coagulation system.He was diagnosed with drug-induced liver failure combined with TMA.After plasma exchange combined with hemoperfusion,pulse therapy with high-dose methylprednisolone,and blood transfusion,his liver function deteriorated,and finally,he died.CONCLUSION ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.展开更多
The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neuro...The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.展开更多
Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dent...Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18–20 hours. Sodium valproate(100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day(4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.展开更多
Objective:To explore the effects of sodium valproate combined with levetiracetam in the treatment of children epilepsy,and its influences on serum S-100βand high mobility group box-1(HMGB-1)in children with epilepsy....Objective:To explore the effects of sodium valproate combined with levetiracetam in the treatment of children epilepsy,and its influences on serum S-100βand high mobility group box-1(HMGB-1)in children with epilepsy.Methods:A total of 160 children who were diagnosed as epilepsy in Baogang Hospital of Inner Mongolia from July 2016 to October 2018 were selected as research objects.They were randomly divided into the study group(n=80)and the control group(n=80)by the random number table method,i.e.,they were treated with sodium valproate combined with levetiracetam and sodium valproate alone,respectively.After 16 weeks of treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge were evaluated,and chi-square test was used for statistical comparison.The related indicators,including serum tumor necrosis factor-(TNF-α),hypersensitive C-reactive protein(hs-CRP),homocysteine(Hcy),haematocrit(HCT),erythrocyte sedimentation rate(ESR),serum S-100βand HMGB-1,were measured before and after treatment.Paired t-test was used for the comparison in the above indicators within a group before and after treatment;group t-test was used for the comparison between two groups.Chi-square test was used for the comparison in the rate of adverse reactions during treatment between two groups.The study was approved by Ethics Committee of Baogang Hospital(Approval No.:BG201606073),and all children’s guardians were required to sign informed consent forms for clinical study.There were no statistically significant differences between two groups in general clinical data(p>0.05),such as sex constituent ratio,age,the course of disease,the frequency of epileptic seizure per year before treatment,the incidence of epileptiform discharge before treatment and the constituent ratio of types of epileptic seizure,etc.Results:1)After treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge in the study group were 92.5%(74/80)and 85.0%(68/80)respectively,which were both significantly higher than those in the control group[68.8%(55/80)and 58.8%(47/80)],and the differences were statistically significant(Х^(2)=14.444,13.635;p<0.001).2)In the study group,the levels of serum TNF-α,hs-CRP and Hcy,as well as HCT and ESR after treatment were(53.1±14.0)pg/ml,(5.0±2.5)mg/L,(12.5±3.1)μmol/L,(38.1±5.1)%and(3.0±0.5)mm/h respectively,which were all significantly lower than those[(107.9±17.8)pg/ml,(10.1±2.5)mg/L,(42.2±5.8)μmol/L,(45.3±4.5)%and(5.2±0.6)mm/h]before treatment,and all the differences were statistically significant(t=21.644,12.902,40.393,9.468,25.194;p<0.001).In the control group,the levels of serum TNF-α,hs-CRP and Hcy,as well as HCT and ESR after treatment were(60.6±17.8)pg/ml,(8.2±2.2)mg/L,(15.2±3.1)μmol/L,(40.2±3.4)%and(4.5±0.6)mm/h respectively,which were all significantly lower than those[(112.4±14.3)pg/ml,(9.3±3.8)mg/L,(41.1±2.8)μmol/L,(44.6±5.5)%and(5.4±0.8)mm/h]before treatment,and all the differences were statistically significant(t=20.292,2.241,55.456,3.320,8.050;p<0.05).After treatment,the above indicators in the study group were all significantly lower than those in the control group,and all the differences were statistically significant(t=2.962,8.595,5.508,3.064,17.178;p<0.05).3)In the study group,the levels of serum S-100βand HMGB-1 after treatment were(0.65±0.38)μg/L and(5.3±2.4)μg/L respectively,which were significantly lower than those[(0.91±0.32)μg/L and(8.1±2.0)μg/L]before treatment,and the differences were statistically significant(t=4.681,8.020;p<0.001).In the control group,the levels of serum S-100βand HMGB-1 after treatment were(0.78±0.27)μg/L and(6.4±2.2)μg/L respectively,which were significantly lower than those[(0.88±0.25)μg/L and(7.9±1.7)μg/L]before treatment,and the differences were statistically significant(t=2.431,p=.016;t=4.826,p<0.001).After treatment,the levels of serum S-100βand HMGB-1 in the study group were significantly lower than those in the control group,and the differences were statistically significant(t=2.495,p=.014;t=2.840,p=.005).4)There was no significant difference between two groups in the rate of adverse reactions,such as nausea,vomiting,poor appetite,dizziness,drowsiness,hepatic and renal injury during treatment(p>0.05).Conclusions:The efficacy of sodium valproate combined with levetiracetam is obviously better than that of sodium valproate alone in the treatment of children epilepsy.The children patients’serum S-100βand HMGB-1 are more significantly reduced,resulting in a lower rate of adverse reactions,which has a certain clinical value.展开更多
BACKGROUND： Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice. ...BACKGROUND： Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice. Whether the fact that differences in drug efficacy and time-effect of different doses of valproate and different types of sustained-release valproate tablets at the same concentration can be quantitatively reflected by determining the changes in convulsive threshold pre- and post-administration in rat models of determining the convulsive threshold developed by direct cortical electrical stimulation remains unclear. OBJECTIVE： This study aimed to compare the drug efficacy and time-effect among magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono in the treatment of epilepsy by determining the convulsive threshold of rat models created by direct cortical electrical stimulation, and human serum drug concentration before and after administration. DESIGN： A controlled observational experiment. SETTING： Research Institute of Epilepsy, Shanxi Medical University. MATERIALS： Adult health male SD rats of clean grade, weighing 200 - 220 g, provided by the Laboratory Animal Center of Shanxi Medical University. The protocol was carried out in accordance with requests from Animal Ethics Committees for guidance. Magnesium valproate （Lot No. 041004） and sustained-release magnesium valproate tablet （Lot No. 050501） were produced in Hunan Xiangzhong Pharmaceutical Co., Ltd. METHODS： This study was carried out in the Laboratory for Epilepsy, Shanxi Medical University between June and August 2005. （1）All the SD rats were created into models for determining cortical convulsive threshold. They were randomly divided into 4 groups with 20 rats in each： magnesium valproate tablet group, sustained-release magnesium valproate tablet group, depakine chrono group and control group. After being modeled, the rats in the first 3 groups were intragastrically administrated with magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono, respectively, while the control group were intragastrically administrated with the same volume of normal saline. （2）Convulsive threshold of each fasting rat was determined 0.5 hour before, and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 and 24 hours after single administration, separately. （3） Convulsive threshold was determined repeatedly 2 weeks after single administration. Each rat was administrated two times daily successively. Convulsive threshold was determined 0.5 hour before, and 0.5, 2.5, 7 and 12 hours after administration, separately. （4）Hepatic and renal tissues were harvested for pathological examination after 1 month of administration. （5）Nine healthy voluntary medical stuffs were recruited in this study. Written informed consents of experiment were obtained each involved subject. The study was given an approval by the Ethics Committee of Shanxi Medical University. According to the scheme, the 9 volunteers were randomly assigned into 3 groups, in which, volunteers were asked to take magnesium valproate 500 g, sustained-release magnesium valproate tablet 500 g and depakine chrono 500 g, respectively, in the morning under the condition of fasting. Serum drug concentration of each drug was determined by fluorescence polarization immunoassay at different time points. MAIN OUTCOME MEASURES： （2） Rat convulsive threshold after single and repeated administrations. （2）Hepatic and renal pathological examination results. （3） Serum drug concentration in vivo. RESULTS：（4）Rat convulsive threshold after single and repeated administrations： Drug efficacy in the magnesium valproate tablet group reached to a peak level 1 to 2 hours after single administration, and was obviously higher than that in the other groups 1 hour after administration （P 〈 0.05）. Drug efficacy in the sustained-release magnesium valproate tablet group and depakine chrono group both reached to a peak level 7 hours after administration, and was significantly higher than that in the control group （P 〈 0.05）. After repeated administrations, the average peak valley deviation of the convulsive threshold in the magnesium valproate tablet group was 120- 150 μ A, which was 2 and 2.5 times as that in the sustained-release magnesium valproate tablet group and depakine chrono group, respectively. After repeated administrations for 10 times, convulsive threshold was increased by 440 μ A in the sustained-release magnesium valproate tablet group, and by 230 μ A in the depakine chrono group in comparison with before administration. （2） Hepatic and renal pathological examination results： No obvious differences in hepatic and renal impairment were found among the 4 groups after I month of administration successively. （3） Serum drug concentration in vivo： Serum-drug concentration of magnesium valproate was increased fast and reached to a peak level 0.5 - 2 hours after administration, remained at a relatively stable level 2 - 4 hours after administration, and then was slowly decreased. The drug efficacy of sustained-release magnesium valproate tablet and depakine chrono was slowly released 1 - 6 hours after administration, reached to a peak level at about 7 hours, and could last for about 16 hours. CONCLUSION： Magnesium valproate has a rapid onset and offset of action. Sustained-release magnesium valproate tablet has a slow onset but long duration of drug efficacy. Depakine chrono can be easier to be absorbed than sustained-release magnesium valproate tablet, but its long-term effect on improving the convulsive threshold is inferior to sustained-release magnesium valproate tablet.展开更多
BACKGROUND: Sodium valproate (VPA) is used to be an effective anti-epileptic drug. VPA possesses the characteristics of penetrating rapidly through the blood-brain barrier (BBB) and increasing levels of Bcl-2 and grow...BACKGROUND: Sodium valproate (VPA) is used to be an effective anti-epileptic drug. VPA possesses the characteristics of penetrating rapidly through the blood-brain barrier (BBB) and increasing levels of Bcl-2 and growth cone-associated protein (GAP) 43 in spinal cord. OBJECTIVE: To observe the effect of VPA on Bcl-2 expression and motor neuronal apoptosis in spinal cord of rats following sciatic nerve transection. DESIGN: Randomized controlled experiment. SETTING: Department of Hand Surgery and Microsurgery, Wuhan Puai Hospital. MATERIALS: A total of 30 male healthy SD rats of clean grade and with the body mass of 180-220 g were provided by Experimental Animal Center of Medical College of Wuhan University. Sodium Valproate Tablets were purchases from Hengrui Pharmaceutical Factory, Jiangsu. METHODS: The experiment was performed in the Central Laboratory of Wuhan Puai Hospital and Medical College of Wuhan University from February to May 2006. Totally 30 rats were randomly divided into two groups: treatment group (n =15) and model group (n =15). Longitudinal incision along backside of right hind limbs of rats was made to expose sciatic nerves, which were sharply transected 1 cm distal to the inferior margin of piriform muscle after nerve liberation under operation microscope to establish sciatic nerve injury rat models. Sodium Valproate Tablets were pulverized and diluted into 50 g/L suspension with saline. On the day of operation, the rats in the treatment group received 6 mL/kg VPA suspension by gastric perfusion, once a day, whereas model group received 10 mL/kg saline by gastric perfusion, once a day. L4-6 spinal cords were obtained at days 1, 4, 7, 14 and 28 after operation, respectively. Terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique and immunohistochemical method (SP method) were used to detect absorbance (A) of neurons with positive Bcl-2 expression. Apoptotic rate of cells (number of apoptotic cells/total number of cells×100%) was calculated. MAIN OUTCOME MEASURES: A value of neurons with positive Bcl-2 expression and apoptotic rate in spinal cord of rats in the two groups. RESULTS: A total of 30 SD rats were involved in the result analysis. ①expression of positive Bcl-2 neurons: A value of positive Bcl-2 neurons were 0.71±0.02, 0.86±0.04, 1.02±0.06 at days 4, 7 and 14, respectively after operation in the treatment group, which were obviously higher than those in the model group (0.62±0.03, 0.71±0.05, 0.89±0.04, t = 3.10-4.50, P < 0.05). ②apoptotic result of motor neurons: Apoptotic rate of motor neurons in spinal cord was (6.91±0.89)% and (15.12±2.34)% at days 7 and 14 in the treatment group, which was significantly lower than those in the model group [(9.45±1.61)%, (19.35±0.92)%, t = 2.39, 3.03. P < 0.05]. CONCLUSION: VPA can increase expression of Bcl-2 in spinal cord and reduce neuronal apoptosis in rats following sciatic nerve injury, and has protective effect on motor neuron in spinal cord of rats.展开更多
Objective: To investigate the effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis as well as inflammatory response in patients with intractable epilepsy. Methods: A total of 70 ...Objective: To investigate the effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis as well as inflammatory response in patients with intractable epilepsy. Methods: A total of 70 patients with intractable epilepsy who were treated in our hospital between August 2013 and October 2016 were divided into routine group (n=35) and study group (n=35) by random number table method, routine group received sodium valproate therapy and study group received lamotrigine combined with sodium valproate therapy. The differences in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors between the two groups. After treatment, serum BDNF and NGF levels of study group were higher than those of routine group;serum Bcl-2, Fas and FasL levels of study group were lower than those of routine group whereas Bax level was higher than that of routine group;serum IL-1β, IL-6 and PGE2 levels of study group were lower than those of routine group. Conclusion: Lamotrigine combined with sodium valproate therapy can effectively increase the neurotrophy, inhibit the nerve apoptosis and reduce the systemic inflammatory response in patients with intractable epilepsy.展开更多
Objective:To explore the effect of sodium valproate retard tablet on the oxidative stress system, cognitive function, and thyroid hormone level in patients with epilepsy.Methods:A total of 68 patients with epilepsy we...Objective:To explore the effect of sodium valproate retard tablet on the oxidative stress system, cognitive function, and thyroid hormone level in patients with epilepsy.Methods:A total of 68 patients with epilepsy were included in the study and randomized into the treatment group and the control group with 34 cases in each group. The patients in the treatment group were given sodium valproate retard tablets, while the patients in the control group were given carbamazepine. The patients in the two groups were treated continuously for 6 months. The oxidative stress indicators and thyroid hormone level before and after treatment in the two groups were detected and compared. MMSE was used to evaluate the cognitive function in the two groups.Results: MPO, SOD, CAT, and GSH-Px levels after treatment in the two groups were significantly reduced when compared with before treatment, while MDA level was significantly elevated. The improvement of the above indicators after treatment in the treatment group was significantly superior to that in the control group. FT3 and FT4 levels after treatment in the control group were significantly reduced when compared with before treatment, but were significantly lower than those in the treatment group. MMSE score 3 and 6 months after treatment in the two groups was significantly elevated when compared with before treatment. MMSE score at each timing point after treatment in the treatment group was significantly higher than that in the control group.Conclusions: The sodium valproate has a small effect on the balance of oxidation and anti-oxidation in patients with epilepsy, and can significantly improve the cognitive function.展开更多
Background Late adverse reactions associated with the combined therapy of valproate and lamotrigine are infrequently documented within the Chinese population.Case presentation This case report describes a 54-year-old ...Background Late adverse reactions associated with the combined therapy of valproate and lamotrigine are infrequently documented within the Chinese population.Case presentation This case report describes a 54-year-old female patient who developed adverse reactions following long-term therapy with valproate and lamotrigine,with symptoms emerging fve months after the fnal adjustment of her antiseizure regimen.The patient presented with symptoms of dizziness,ataxia,nystagmus,and postural tremors.Following blood drug concentration monitoring and subsequent minor dosage adjustments to the antiseizure regimen without medication withdrawal,the patient’s symptoms were successfully resolved.Conclusions This article underscores the importance of vigilance among clinicians regarding the potential for late adverse reactions and advocates for the proactive monitoring of blood drug concentrations.展开更多
Background Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the anti...Background Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the antitumor effects of sodium valproate is limited; therefore, we explored the mechanisms of action of sodium valproate in the human hepatoblastoma cell line, HepG2.Methods The effects of sodium valproate on the proliferation of HepG2 cells were evaluated by the Walsh-sohema transform and colony formation assays. Sodium valproate-induced apoptosis in HepG2 cells was investigated with fluorescence microscopy to detect morphological changes; by flow cytometry to calculate DNA ploidy and apoptotic cell percentages; with Western blotting analyses to determine c-Jun N-terminal kinases （JNK）, p-JNK, Bcl-2, Bax, and caspase-3 and-9 protein expression levels; and using JC-1 fluorescence microscopy to detect the membrane potential of mitochondria. Statistical analyses were performed using one-way analysis of variance by SPSS 13.0 software.Results Our results indicated that sodium valproate treatment inhibited the proliferation of HepG2 cells in a dose-dependent manner. Sodium valproate induced apoptosis in HepG2 cells as it： caused morphologic changes associated with apoptosis, including condensed and fragmented chromatin; increased the percentage of hypodiploid cells in a dose-dependent manner; increased the percentage of annexin Ⅴ-positive/propidium iodide-negative cells from 9.52％ to 74.87％; decreased JNK and increased phosphate-JNK protein expression levels; reduced the membrane potential of mitochondria; decreased the ratio of Bcl-2/Bax; and activated caspases-3 and-9.Conclusion Sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.展开更多
Background To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury(TBI).Methods A total of 95 patients with TBI were recruited fro...Background To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury(TBI).Methods A total of 95 patients with TBI were recruited from 2017 to 2020.They were randomized into three groups:levetiracetam(LEV)group(n=30)receiving LEV treatment(500 mg,bid,po);valproate group(n=32)receiving sodium valproate(500 mg/d,once daily,po);and control group(n=33)receiving no anti-seizure medication.LEV and valproate were given to corresponding groups within seven days after TBI,and the administration lasted for one month.The incidence of epilepsy and adverse events were evaluated at 7 days and 12 months post-TBI.Results The cumulative incidences of late post-traumatic seizures at the 12-month follow-up in the LEV,valproate,and control groups were 3.33%,12.50%and 15.63%,respectively.The cumulative incidence of late post-traumatic seizures in the LEV group was significantly lower than those in the valproate and control groups(P<0.05).The cumulative incidence of late post-traumatic seizure in the valproate group was not significantly different from that in the control group(P>0.05).Conclusions LEV can reduce the cumulative incidence of late post-traumatic seizures,whereas valproate can not.展开更多
Background: Although treatment guidelines for bipolar disorder in many countries commonly include lithium carbonate joint with sodium valproate, this combination is not effective for all patients. Moreover, some adver...Background: Although treatment guidelines for bipolar disorder in many countries commonly include lithium carbonate joint with sodium valproate, this combination is not effective for all patients. Moreover, some adverse reactions related to this treatment, neurotoxicity and interaction with other drugs justify and call for a new reviewing of the issue. Methods: Evidence base for the interactions of combined drugs, the metabolic features, action mechanism, efficacy and side effects of these treatment combinations were reviewed. Considerable attention was given to the relationship of the mutual action of these drugs with their clinical efficacy but also their side effects. Results: The efficacy of combination therapy of lithium with valproate for treatment and prevention of mania were superior to monotherapy of lithium or valproate. Conclusion: Double mood stabilizer therapy is the best relative treatment for patients with bipolar disorder, especially mania and related episodes.展开更多
AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years ...AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement(DRESS) in 18(75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis(SJS/TEN) overlap and TEN in 2(8.3%) patients each, SJS and lichenoid drug eruption in 1(4.2%) patient each, respectively. The implicated drugs were phenytoin in 14(58.3%), carbamazepine in 9(37.5%), phenobarbitone in 2(8.3%), and lamotrigine in 1(4.7%) patients,respectively. Twelve(50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6(50%), phenytoin alone in 4(33.3%), phenobarbitone alone in 1(8.3%), and both phenytoin and phenobarbitone in 1(8.33%) patients, respectively. Cross-reactions occurred in 11(92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three(75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.展开更多
基金supported by the National Natural Science Foundation of China(82160803)High level Innovative Talents Project of Guizhou Province(Guizhou Science and Technology Cooperation Platform Talents-GCC[2023]077).
文摘Background:To explore the antioxidant capacity ofα-asarone(ARE)in mice models of sodium valproate(SV)-induced liver injury,and to elucidate the underlying mechanism of ARE in liver injury treatment.Methods:Network pharmacology and molecular docking were used to predict ARE’s potential pharmacological mechanisms in treating drug-induced liver injury.AML12 cell model was used to evaluate the antioxidant stress activation of ARE.In the evaluation of antioxidant activity,ARE was tested for its ability to scavenge hydroxyl radical(OH)radicals,2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS+),and 1,1-diphenyl-2-picrylhydrazyl(DPPH),with vitamin C serving as the positive control.And thirty-six male mice were divided into six groups.Group I,the control,received saline.The other five groups received oral doses of 500 mg/kg/b.w.of SV daily for 14 days.Group II received only SV.Group III received the hepatic protectant bifendate at 100 mg/kg/b.w.,while groups IV,V,and VI were treated with 20,40,and 80 mg/kg/b.w.of ARE,respectively,also for 14 days.After sacrifice,liver and blood samples were collected for biochemical or metabolomic analysis.Results:ARE significantly reduced the levels of reactive oxygen species and activated the Keap1/Nrf2 signaling pathway in liver injury AML12 cells.ARE demonstrated dose-dependent scavenging activity in DPPH,ABTS+,and OH assays.It lowered serum alanine aminotransferase and aspartate aminotransferase levels,increased glutathione peroxidase and superoxide dismutase activity in liver tissue,and reduced malondialdehyde content.Metabolomic analysis showed that ARE restored twenty liver metabolites to control levels and enriched three pathways(arginine biosynthesis,sucrose and starch metabolism,and biotin metabolism)with shared differential metabolites.Conclusion:These results shed light on ARE’s mechanism in reducing oxidative stress,suggesting a potential strategy for preventing SV-induced liver disease by modulating metabolic products and enhancing antioxidant capacity.ARE could be a promising drug candidate for its antioxidant and liver-protective effects.
基金supported by a research grant(No.6211)from Shahrekord University of Medical Sciences,Shahrekord,Iran.
文摘Objective:To explore the effect of black radish(Raphanus sativus L.var niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced hepatotoxicity.Methods:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were assessed.Results:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological alterations.The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological changes.Conclusions:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.
基金supported by the Natural Science Foundation of Shanghai(11ZR1421800,12ZR1413800)the Shanghai Jiao Tong University Fund for Interdisciplinary Research for Medical Applications(G08PETZD05)
文摘The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K ＋ concentration （8.5 mmol/L） in the bath, and the effects of the anti-epileptic drug valproate （VPA） on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration （100 μmol/L） suppressed the propagation speed but not the rate or duration of high-K＋-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.
文摘BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming apparent,particularly hepatotoxicity.Herein,we report a case of fatal acute liver failure(ALF)with thrombotic microangiopathy(TMA)caused by treatment with sodium valproate in a patient following surgery for meningioma.CASE SUMMARY A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue,severe jaundice accompanied by oliguria,soy sauce-colored urine,and ecchymosis.His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level,severe liver and kidney dysfunction,and disturbance of the coagulation system.He was diagnosed with drug-induced liver failure combined with TMA.After plasma exchange combined with hemoperfusion,pulse therapy with high-dose methylprednisolone,and blood transfusion,his liver function deteriorated,and finally,he died.CONCLUSION ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.
基金supported by the National Natural Science Foundation of China,Nos.30772368(to DH),81371034(to XH)the Key Project of Natural Science Foundation of Shaanxi Province,No.2017JZ025(to DH).
文摘The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.
基金supported by the National Natural Science Foundation of China for Youth Science Project,No.81201507(to PW)
文摘Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18–20 hours. Sodium valproate(100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day(4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.
文摘Objective:To explore the effects of sodium valproate combined with levetiracetam in the treatment of children epilepsy,and its influences on serum S-100βand high mobility group box-1(HMGB-1)in children with epilepsy.Methods:A total of 160 children who were diagnosed as epilepsy in Baogang Hospital of Inner Mongolia from July 2016 to October 2018 were selected as research objects.They were randomly divided into the study group(n=80)and the control group(n=80)by the random number table method,i.e.,they were treated with sodium valproate combined with levetiracetam and sodium valproate alone,respectively.After 16 weeks of treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge were evaluated,and chi-square test was used for statistical comparison.The related indicators,including serum tumor necrosis factor-(TNF-α),hypersensitive C-reactive protein(hs-CRP),homocysteine(Hcy),haematocrit(HCT),erythrocyte sedimentation rate(ESR),serum S-100βand HMGB-1,were measured before and after treatment.Paired t-test was used for the comparison in the above indicators within a group before and after treatment;group t-test was used for the comparison between two groups.Chi-square test was used for the comparison in the rate of adverse reactions during treatment between two groups.The study was approved by Ethics Committee of Baogang Hospital(Approval No.:BG201606073),and all children’s guardians were required to sign informed consent forms for clinical study.There were no statistically significant differences between two groups in general clinical data(p>0.05),such as sex constituent ratio,age,the course of disease,the frequency of epileptic seizure per year before treatment,the incidence of epileptiform discharge before treatment and the constituent ratio of types of epileptic seizure,etc.Results:1)After treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge in the study group were 92.5%(74/80)and 85.0%(68/80)respectively,which were both significantly higher than those in the control group[68.8%(55/80)and 58.8%(47/80)],and the differences were statistically significant(Х^(2)=14.444,13.635;p<0.001).2)In the study group,the levels of serum TNF-α,hs-CRP and Hcy,as well as HCT and ESR after treatment were(53.1±14.0)pg/ml,(5.0±2.5)mg/L,(12.5±3.1)μmol/L,(38.1±5.1)%and(3.0±0.5)mm/h respectively,which were all significantly lower than those[(107.9±17.8)pg/ml,(10.1±2.5)mg/L,(42.2±5.8)μmol/L,(45.3±4.5)%and(5.2±0.6)mm/h]before treatment,and all the differences were statistically significant(t=21.644,12.902,40.393,9.468,25.194;p<0.001).In the control group,the levels of serum TNF-α,hs-CRP and Hcy,as well as HCT and ESR after treatment were(60.6±17.8)pg/ml,(8.2±2.2)mg/L,(15.2±3.1)μmol/L,(40.2±3.4)%and(4.5±0.6)mm/h respectively,which were all significantly lower than those[(112.4±14.3)pg/ml,(9.3±3.8)mg/L,(41.1±2.8)μmol/L,(44.6±5.5)%and(5.4±0.8)mm/h]before treatment,and all the differences were statistically significant(t=20.292,2.241,55.456,3.320,8.050;p<0.05).After treatment,the above indicators in the study group were all significantly lower than those in the control group,and all the differences were statistically significant(t=2.962,8.595,5.508,3.064,17.178;p<0.05).3)In the study group,the levels of serum S-100βand HMGB-1 after treatment were(0.65±0.38)μg/L and(5.3±2.4)μg/L respectively,which were significantly lower than those[(0.91±0.32)μg/L and(8.1±2.0)μg/L]before treatment,and the differences were statistically significant(t=4.681,8.020;p<0.001).In the control group,the levels of serum S-100βand HMGB-1 after treatment were(0.78±0.27)μg/L and(6.4±2.2)μg/L respectively,which were significantly lower than those[(0.88±0.25)μg/L and(7.9±1.7)μg/L]before treatment,and the differences were statistically significant(t=2.431,p=.016;t=4.826,p<0.001).After treatment,the levels of serum S-100βand HMGB-1 in the study group were significantly lower than those in the control group,and the differences were statistically significant(t=2.495,p=.014;t=2.840,p=.005).4)There was no significant difference between two groups in the rate of adverse reactions,such as nausea,vomiting,poor appetite,dizziness,drowsiness,hepatic and renal injury during treatment(p>0.05).Conclusions:The efficacy of sodium valproate combined with levetiracetam is obviously better than that of sodium valproate alone in the treatment of children epilepsy.The children patients’serum S-100βand HMGB-1 are more significantly reduced,resulting in a lower rate of adverse reactions,which has a certain clinical value.
文摘BACKGROUND： Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice. Whether the fact that differences in drug efficacy and time-effect of different doses of valproate and different types of sustained-release valproate tablets at the same concentration can be quantitatively reflected by determining the changes in convulsive threshold pre- and post-administration in rat models of determining the convulsive threshold developed by direct cortical electrical stimulation remains unclear. OBJECTIVE： This study aimed to compare the drug efficacy and time-effect among magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono in the treatment of epilepsy by determining the convulsive threshold of rat models created by direct cortical electrical stimulation, and human serum drug concentration before and after administration. DESIGN： A controlled observational experiment. SETTING： Research Institute of Epilepsy, Shanxi Medical University. MATERIALS： Adult health male SD rats of clean grade, weighing 200 - 220 g, provided by the Laboratory Animal Center of Shanxi Medical University. The protocol was carried out in accordance with requests from Animal Ethics Committees for guidance. Magnesium valproate （Lot No. 041004） and sustained-release magnesium valproate tablet （Lot No. 050501） were produced in Hunan Xiangzhong Pharmaceutical Co., Ltd. METHODS： This study was carried out in the Laboratory for Epilepsy, Shanxi Medical University between June and August 2005. （1）All the SD rats were created into models for determining cortical convulsive threshold. They were randomly divided into 4 groups with 20 rats in each： magnesium valproate tablet group, sustained-release magnesium valproate tablet group, depakine chrono group and control group. After being modeled, the rats in the first 3 groups were intragastrically administrated with magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono, respectively, while the control group were intragastrically administrated with the same volume of normal saline. （2）Convulsive threshold of each fasting rat was determined 0.5 hour before, and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 and 24 hours after single administration, separately. （3） Convulsive threshold was determined repeatedly 2 weeks after single administration. Each rat was administrated two times daily successively. Convulsive threshold was determined 0.5 hour before, and 0.5, 2.5, 7 and 12 hours after administration, separately. （4）Hepatic and renal tissues were harvested for pathological examination after 1 month of administration. （5）Nine healthy voluntary medical stuffs were recruited in this study. Written informed consents of experiment were obtained each involved subject. The study was given an approval by the Ethics Committee of Shanxi Medical University. According to the scheme, the 9 volunteers were randomly assigned into 3 groups, in which, volunteers were asked to take magnesium valproate 500 g, sustained-release magnesium valproate tablet 500 g and depakine chrono 500 g, respectively, in the morning under the condition of fasting. Serum drug concentration of each drug was determined by fluorescence polarization immunoassay at different time points. MAIN OUTCOME MEASURES： （2） Rat convulsive threshold after single and repeated administrations. （2）Hepatic and renal pathological examination results. （3） Serum drug concentration in vivo. RESULTS：（4）Rat convulsive threshold after single and repeated administrations： Drug efficacy in the magnesium valproate tablet group reached to a peak level 1 to 2 hours after single administration, and was obviously higher than that in the other groups 1 hour after administration （P 〈 0.05）. Drug efficacy in the sustained-release magnesium valproate tablet group and depakine chrono group both reached to a peak level 7 hours after administration, and was significantly higher than that in the control group （P 〈 0.05）. After repeated administrations, the average peak valley deviation of the convulsive threshold in the magnesium valproate tablet group was 120- 150 μ A, which was 2 and 2.5 times as that in the sustained-release magnesium valproate tablet group and depakine chrono group, respectively. After repeated administrations for 10 times, convulsive threshold was increased by 440 μ A in the sustained-release magnesium valproate tablet group, and by 230 μ A in the depakine chrono group in comparison with before administration. （2） Hepatic and renal pathological examination results： No obvious differences in hepatic and renal impairment were found among the 4 groups after I month of administration successively. （3） Serum drug concentration in vivo： Serum-drug concentration of magnesium valproate was increased fast and reached to a peak level 0.5 - 2 hours after administration, remained at a relatively stable level 2 - 4 hours after administration, and then was slowly decreased. The drug efficacy of sustained-release magnesium valproate tablet and depakine chrono was slowly released 1 - 6 hours after administration, reached to a peak level at about 7 hours, and could last for about 16 hours. CONCLUSION： Magnesium valproate has a rapid onset and offset of action. Sustained-release magnesium valproate tablet has a slow onset but long duration of drug efficacy. Depakine chrono can be easier to be absorbed than sustained-release magnesium valproate tablet, but its long-term effect on improving the convulsive threshold is inferior to sustained-release magnesium valproate tablet.
文摘BACKGROUND: Sodium valproate (VPA) is used to be an effective anti-epileptic drug. VPA possesses the characteristics of penetrating rapidly through the blood-brain barrier (BBB) and increasing levels of Bcl-2 and growth cone-associated protein (GAP) 43 in spinal cord. OBJECTIVE: To observe the effect of VPA on Bcl-2 expression and motor neuronal apoptosis in spinal cord of rats following sciatic nerve transection. DESIGN: Randomized controlled experiment. SETTING: Department of Hand Surgery and Microsurgery, Wuhan Puai Hospital. MATERIALS: A total of 30 male healthy SD rats of clean grade and with the body mass of 180-220 g were provided by Experimental Animal Center of Medical College of Wuhan University. Sodium Valproate Tablets were purchases from Hengrui Pharmaceutical Factory, Jiangsu. METHODS: The experiment was performed in the Central Laboratory of Wuhan Puai Hospital and Medical College of Wuhan University from February to May 2006. Totally 30 rats were randomly divided into two groups: treatment group (n =15) and model group (n =15). Longitudinal incision along backside of right hind limbs of rats was made to expose sciatic nerves, which were sharply transected 1 cm distal to the inferior margin of piriform muscle after nerve liberation under operation microscope to establish sciatic nerve injury rat models. Sodium Valproate Tablets were pulverized and diluted into 50 g/L suspension with saline. On the day of operation, the rats in the treatment group received 6 mL/kg VPA suspension by gastric perfusion, once a day, whereas model group received 10 mL/kg saline by gastric perfusion, once a day. L4-6 spinal cords were obtained at days 1, 4, 7, 14 and 28 after operation, respectively. Terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique and immunohistochemical method (SP method) were used to detect absorbance (A) of neurons with positive Bcl-2 expression. Apoptotic rate of cells (number of apoptotic cells/total number of cells×100%) was calculated. MAIN OUTCOME MEASURES: A value of neurons with positive Bcl-2 expression and apoptotic rate in spinal cord of rats in the two groups. RESULTS: A total of 30 SD rats were involved in the result analysis. ①expression of positive Bcl-2 neurons: A value of positive Bcl-2 neurons were 0.71±0.02, 0.86±0.04, 1.02±0.06 at days 4, 7 and 14, respectively after operation in the treatment group, which were obviously higher than those in the model group (0.62±0.03, 0.71±0.05, 0.89±0.04, t = 3.10-4.50, P < 0.05). ②apoptotic result of motor neurons: Apoptotic rate of motor neurons in spinal cord was (6.91±0.89)% and (15.12±2.34)% at days 7 and 14 in the treatment group, which was significantly lower than those in the model group [(9.45±1.61)%, (19.35±0.92)%, t = 2.39, 3.03. P < 0.05]. CONCLUSION: VPA can increase expression of Bcl-2 in spinal cord and reduce neuronal apoptosis in rats following sciatic nerve injury, and has protective effect on motor neuron in spinal cord of rats.
文摘Objective: To investigate the effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis as well as inflammatory response in patients with intractable epilepsy. Methods: A total of 70 patients with intractable epilepsy who were treated in our hospital between August 2013 and October 2016 were divided into routine group (n=35) and study group (n=35) by random number table method, routine group received sodium valproate therapy and study group received lamotrigine combined with sodium valproate therapy. The differences in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors between the two groups. After treatment, serum BDNF and NGF levels of study group were higher than those of routine group;serum Bcl-2, Fas and FasL levels of study group were lower than those of routine group whereas Bax level was higher than that of routine group;serum IL-1β, IL-6 and PGE2 levels of study group were lower than those of routine group. Conclusion: Lamotrigine combined with sodium valproate therapy can effectively increase the neurotrophy, inhibit the nerve apoptosis and reduce the systemic inflammatory response in patients with intractable epilepsy.
文摘Objective:To explore the effect of sodium valproate retard tablet on the oxidative stress system, cognitive function, and thyroid hormone level in patients with epilepsy.Methods:A total of 68 patients with epilepsy were included in the study and randomized into the treatment group and the control group with 34 cases in each group. The patients in the treatment group were given sodium valproate retard tablets, while the patients in the control group were given carbamazepine. The patients in the two groups were treated continuously for 6 months. The oxidative stress indicators and thyroid hormone level before and after treatment in the two groups were detected and compared. MMSE was used to evaluate the cognitive function in the two groups.Results: MPO, SOD, CAT, and GSH-Px levels after treatment in the two groups were significantly reduced when compared with before treatment, while MDA level was significantly elevated. The improvement of the above indicators after treatment in the treatment group was significantly superior to that in the control group. FT3 and FT4 levels after treatment in the control group were significantly reduced when compared with before treatment, but were significantly lower than those in the treatment group. MMSE score 3 and 6 months after treatment in the two groups was significantly elevated when compared with before treatment. MMSE score at each timing point after treatment in the treatment group was significantly higher than that in the control group.Conclusions: The sodium valproate has a small effect on the balance of oxidation and anti-oxidation in patients with epilepsy, and can significantly improve the cognitive function.
基金funded by the Basic Research Program of Shanxi Provincial Department of Science and Technology(202203021221299).
文摘Background Late adverse reactions associated with the combined therapy of valproate and lamotrigine are infrequently documented within the Chinese population.Case presentation This case report describes a 54-year-old female patient who developed adverse reactions following long-term therapy with valproate and lamotrigine,with symptoms emerging fve months after the fnal adjustment of her antiseizure regimen.The patient presented with symptoms of dizziness,ataxia,nystagmus,and postural tremors.Following blood drug concentration monitoring and subsequent minor dosage adjustments to the antiseizure regimen without medication withdrawal,the patient’s symptoms were successfully resolved.Conclusions This article underscores the importance of vigilance among clinicians regarding the potential for late adverse reactions and advocates for the proactive monitoring of blood drug concentrations.
基金This study was supported by grants from Sci-Tech Project Foundation of Guangdong Province, China （No. 2009B080701051） and the National Natural Science Foundation of China （No. 30973811）.
文摘Background Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the antitumor effects of sodium valproate is limited; therefore, we explored the mechanisms of action of sodium valproate in the human hepatoblastoma cell line, HepG2.Methods The effects of sodium valproate on the proliferation of HepG2 cells were evaluated by the Walsh-sohema transform and colony formation assays. Sodium valproate-induced apoptosis in HepG2 cells was investigated with fluorescence microscopy to detect morphological changes; by flow cytometry to calculate DNA ploidy and apoptotic cell percentages; with Western blotting analyses to determine c-Jun N-terminal kinases （JNK）, p-JNK, Bcl-2, Bax, and caspase-3 and-9 protein expression levels; and using JC-1 fluorescence microscopy to detect the membrane potential of mitochondria. Statistical analyses were performed using one-way analysis of variance by SPSS 13.0 software.Results Our results indicated that sodium valproate treatment inhibited the proliferation of HepG2 cells in a dose-dependent manner. Sodium valproate induced apoptosis in HepG2 cells as it： caused morphologic changes associated with apoptosis, including condensed and fragmented chromatin; increased the percentage of hypodiploid cells in a dose-dependent manner; increased the percentage of annexin Ⅴ-positive/propidium iodide-negative cells from 9.52％ to 74.87％; decreased JNK and increased phosphate-JNK protein expression levels; reduced the membrane potential of mitochondria; decreased the ratio of Bcl-2/Bax; and activated caspases-3 and-9.Conclusion Sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.
基金funded by the Scientific Research Fund of China Association Against Epilepsy(No 2012002).
文摘Background To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury(TBI).Methods A total of 95 patients with TBI were recruited from 2017 to 2020.They were randomized into three groups:levetiracetam(LEV)group(n=30)receiving LEV treatment(500 mg,bid,po);valproate group(n=32)receiving sodium valproate(500 mg/d,once daily,po);and control group(n=33)receiving no anti-seizure medication.LEV and valproate were given to corresponding groups within seven days after TBI,and the administration lasted for one month.The incidence of epilepsy and adverse events were evaluated at 7 days and 12 months post-TBI.Results The cumulative incidences of late post-traumatic seizures at the 12-month follow-up in the LEV,valproate,and control groups were 3.33%,12.50%and 15.63%,respectively.The cumulative incidence of late post-traumatic seizures in the LEV group was significantly lower than those in the valproate and control groups(P<0.05).The cumulative incidence of late post-traumatic seizure in the valproate group was not significantly different from that in the control group(P>0.05).Conclusions LEV can reduce the cumulative incidence of late post-traumatic seizures,whereas valproate can not.
文摘Background: Although treatment guidelines for bipolar disorder in many countries commonly include lithium carbonate joint with sodium valproate, this combination is not effective for all patients. Moreover, some adverse reactions related to this treatment, neurotoxicity and interaction with other drugs justify and call for a new reviewing of the issue. Methods: Evidence base for the interactions of combined drugs, the metabolic features, action mechanism, efficacy and side effects of these treatment combinations were reviewed. Considerable attention was given to the relationship of the mutual action of these drugs with their clinical efficacy but also their side effects. Results: The efficacy of combination therapy of lithium with valproate for treatment and prevention of mania were superior to monotherapy of lithium or valproate. Conclusion: Double mood stabilizer therapy is the best relative treatment for patients with bipolar disorder, especially mania and related episodes.
文摘AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement(DRESS) in 18(75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis(SJS/TEN) overlap and TEN in 2(8.3%) patients each, SJS and lichenoid drug eruption in 1(4.2%) patient each, respectively. The implicated drugs were phenytoin in 14(58.3%), carbamazepine in 9(37.5%), phenobarbitone in 2(8.3%), and lamotrigine in 1(4.7%) patients,respectively. Twelve(50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6(50%), phenytoin alone in 4(33.3%), phenobarbitone alone in 1(8.3%), and both phenytoin and phenobarbitone in 1(8.33%) patients, respectively. Cross-reactions occurred in 11(92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three(75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.
