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Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 298-306页

作者： Mohammad Hadi Zarei Sami Akbulut Maryam Zafari Elham Saghaei Zahra Lorigooini Hossein AminiKhoei Somaye Khosravi Elham Bijad Medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran Department of Liver Transplant Institute and Biostatistics Inonu University Faculty of Medicine44280MalatyaTurkey Student Research Committee Shahrekord University of Medical SciencesShahrekordIran Physiology and Pharmacology Department School of MedicineShahrekord University of Medical SciencesShahrekordIran Department of Anatomical Sciences School of MedicineShahrekord University of Medical SciencesShahrekordIran

Objective:To explore the effect of black radish(Raphanus sativus *** niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced ***: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 ***: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 *** 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 ***: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.

关键词： Black radish Raphanus sativus sodium valproate Hepatotoxicity Oxidative stress Anti-inflammation

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Acute liver failure with thrombotic microangiopathy due to sodium valproate toxicity:A case report

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World Journal of Clinical Cases 2021年第17期9卷 4310-4317页

作者： Xuan Mei Hai-Cong Wu Mei Ruan Li-Rong Cai Department of Hepatobiliary Internal Medicine The 900th Hospital of PLA Joint Logistics Support ForceFuzhou 350025Fujian ProvinceChina Department of Hepatobiliary Internal Medicine The third affiliated people's hospital of FuJian University of traditional Chinese medicineFuzhou 350100Fujian ProvinceChina

BACKGROUND sodium valproate is widely used in the treatment of epilepsy in clinical *** adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming apparent,particularly ***,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 *** 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 *** postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level,severe liver and kidney dysfunction,and disturbance of the coagulation *** was diagnosed with drug-induced liver failure combined with *** plasma exchange combined with hemoperfusion,pulse therapy with high-dose methylprednisolone,and blood transfusion,his liver function deteriorated,and finally,he *** ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.

关键词： sodium valproate Drug-induced liver injury Thrombotic microangiopathy Plasma exchange Organ transplantation Case report

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sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells

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Chinese Medical Journal 2011年第14期124卷 2167-2172页

作者： WANG Wei LIAO Xiao-li CHEN Jing-hong LI Dan-dan LIN Chun-lan YAN Yu-xia TANG Yu-hui JIANG Jian-wei Department of Biochemistry Medical College of Jinan UniversityGuangzhou Guangdong 510632 China State Key Laboratory of Oncology in Southern China Cancer Center Sun Yat-sen University Guangzhou Guangdong 510060China Department of Biochemistry Guangzhou University of Chinese Medicine Guangzhou Guangdong 510006 China

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, *** 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 *** 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 *** sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.

关键词： hepatoblastoma sodium valproate c-Jun N-terminal kinases mitochondria apoptosis

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No effect of acylpeptide hydrolase polymorphisms on pharmacokinetics of sodium valproate in healthy Chinese male volunteers

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中国药理学与毒理学杂志 2019年第10期 816-817页

作者： WEN Zhi-peng Zeng Wen-jing XIAO Jian CHEN Xiao-ping Department of Clinical Pharmacology Xiangya HospitalCentral South University Institute of Clinical Pharmacology Hunan Key Laboratory of Pharmacogenetic Central South University National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South University Department of Pharmacy Xiangya Hospital Central South University

OBJECTIVE sodium valproate（VPA） is one of the most common prescribed antiepileptic drugs（AEDs）. Genetic variation in genes encoding drug-metabolizing enzymes may contribute the inter-individual variability in VPA pharmacokinetics. Our previous study showed that acylpeptide hydrolase（APEH） polymorphisms might affect the VPA plasma concentration in Chinese epilepsy patients by increasing the urinary excretion of valproate-glucuronide（VPA-G）, the major metabolite of VPA. This study aimed to investigate the effects of APEH rs3816877 on the pharmacokinetics of VPA in healthy Chinese male volunteers. METHODS Thirteen subjects enrolled in this clinical trial were genotyped for APEH rs3816877 by polymerase chain reactionrestriction fragment length polymorphism（PCR-RFLP）.All volunteers received an oral dose of 1000 mg of VPA sustain tablets（Depakine, Sanofi）. The peripheral venous blood and urine were sampled for up to 72 h and 24 h post dose, respectively. The concentration of VPA and VPA-G in plasma and urine were determined by the high performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS） system. The pharmacokinetic parameters were calculated using standard non-compartmental model. RESULTS No significantly different C;,T;, t;, CL, Vd, AUC;, and AUC;were observed between APEH rs3816877 C/C group and C/T ***, the subjects carrying rs3816877 C/C genotype were characteristics with significantly higher urinary excretion of VPA-G than those with C/T genotype. CONCLUSION Our study suggested that APEH rs3816877 may have no effect on the pharmacokinetics of VPA in healthy Chinese male volunteers.

关键词： sodium valproate acylpeptide hydrolases pharmacokintics pharmacogenetics

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Effects of sodium valproate combined with levetiracetam in treatment of children epilepsy and its influences on serum S-100βand high mobility group box-1

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Discussion of Clinical Cases 2020年第1期7卷 12-18页

作者： Huimin Li Jinli Hao Hua Chen Yong Meng Department of Pediatrics Baogang HospitalBaotouInner MongoliaChina Department of Pediatrics Surgery the First Affiliated Hospital of Xinxiang Medical CollegeHenan ProvinceChina

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 ***: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 *** 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,*** 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 *** 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 *** 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 ***-square test was used for the comparison in the rate of adverse reactions during treatment between two *** 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 *** 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,***:1)After treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge in the study group were 9

关键词： Epilepsy sodium valproate Levetiracetam S-100 HMGB-1 protein Tumor necrosis factor- Haematocrit Children

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Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

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World Journal of Methodology 2017年第1期7卷 25-32页

作者： TN Shiny Vikram K Mahajan Karaninder S Mehta Pushpinder S Chauhan Ritu Rawat Rajni Sharma Department of Der-matology Venereology and LeprosyDr.R.P.Govt. Medical College

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.

关键词： Anticonvulsant hypersensitivity syndrome Carbamazepine sodium valproate Drug rash with eosinophilia with or without systemic involvement Drug patch test Lamotrigine Phenobarbitone Phenytoin Stevens-Johnsons syndrome Toxic epidermal necrolysis

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