Message Board

Respected readers, authors and reviewers, you can add comments to this page on any questions about the contribution, review,        editing and publication of this journal. We will give you an answer as soon as possible. Thank you for your support!

Name
E-mail
Phone
Title
Content
Verification Code
x Close Forever Close
Volume 35 Issue 1
. 
Turn off MathJax
Article Contents
Article Navigation >  Journal of Pharmaceutical Practice and Service  > 2017  >  35(1): 43-47,53

XIE Xinfang, WEN Yan, GAO Shouhong, YOU Chunhua, CHEN Wansheng, XIONG Xiaojuan. An in vitro study of hepatotoxicity induced by valproic acid and its metabolites[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(1): 43-47,53. doi: 10.3969/j.issn.1006-0111.2017.01.011
Citation: XIE Xinfang, WEN Yan, GAO Shouhong, YOU Chunhua, CHEN Wansheng, XIONG Xiaojuan. An in vitro study of hepatotoxicity induced by valproic acid and its metabolites[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(1): 43-47,53. doi: 10.3969/j.issn.1006-0111.2017.01.011
shu

An in vitro study of hepatotoxicity induced by valproic acid and its metabolites

doi: 10.3969/j.issn.1006-0111.2017.01.011
  • 1.

    Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;College of Chemical and Biological Engineering, Yichun University, Yichun 336000, China

  • 2.

    Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

  • 3.

    College of Chemical and Biological Engineering, Yichun University, Yichun 336000, China

  • Received Date: 2016-05-31
  • Rev Recd Date: 2016-09-29
  • Objective To confirm the hepatotoxicity of valproic acid (VPA) and its metabolites(2-propyl-4-pentenoic acid, 3-hydroxy valproic acid, 5-hydroxy valproic acid) on human liver cells. Methods Cells were divided into control group and VPA-treated group. The control group was conventionally cultured while the VPA-treated group was treated with valproic acid and its metabolites. The rate of cell proliferation was assayed by CCK 8 protocol. The mRNA levels of CYP1A1, CYP1A2, PCNA, Bax and Bcl-2 were measured by real time PCR. The correlated protein levels were measured by Western Blotting. The activity of LDH, AST and ALT were also detected. Results Compared to the control group, with the increases of concentrations and reaction time of VPA and its metabolites, the proliferation rate of L02-cell was reduced, the mRNA and protein levels of CYP1A1, CYP1A2, and Bax was increased, the mRNA and protein level of PCNA and Bcl-2 was decreased, AST, ALT, and LDH were also elevated in the treated group. Conclusion Valproic acid and its metabolites were positively related to hepatotoxicity.
  • [1] Ghodke-Puranik Y, Thorn CF, Lamba JK, et al. Valproic acid pathway:pharmacokinetics and pharmacodynamics[J]. Pharmacogenet Genom 2013, 23(4):236-241.
    [2] 冯亚娟,周建华,吴干斌,等. 丙戊酸代谢相关CYP2C19基因多态性在癫痫患儿体内的分布及治疗个体化研究[J]. 中国实用神经疾病杂志,2015,1(5):49-52.
    [3] 陈蕊,张明. 丙戊酸相关肝损害的治疗进展[J]. 中国新药与临床杂志,2015,34(6):405-409.
    [4] Schmid MM, Freudenmann RW, Keller F, et al. Non-fatal and fatal liver failure associated with valproic acid[J]. Pharmacopsychiatry, 2013, 46(02):63-68.
    [5] Nanau RM, Neuman MG. Adverse drug reactions induced by valproic acid[J]. Clin Biochem, 2013, 46(15):1323-1338.
    [6] Kuzniecky RI, Barkovich AJ. Malformations of cortical development and epilepsy[J]. Brain Dev, 2001, 23(1):2-11.
    [7] 李新林,赵明明,肇丽梅,等. 丙戊酸群体药代动力学研究进展[J]. 实用药物与临床,2014,17(3):345-349.
    [8] Leppik IE,Bimbaum AK. Epilepsy in the elderly[J].Ann N Y Acad Sci,2010,1184:208-224.
    [9] 游春华,高守红,陈万生,等. 群体药代动力学用于丙戊酸钠个体化给药[J]. 第二军医大学学报,2015,36(12):1-4.
    [10] 万长亮,王志纲. 丙戊酸血药浓度的研究进展[J]. 内蒙古医学院学报,2010,32(4):31-35.
    [11] 白向荣,姜德春,王育琴. 基因多态性与丙戊酸的药物代谢[J]. 中国药物依赖性杂志,2007,16(4):241-244.
    [12] 储小曼,郭岑,张丽芬. 丙戊酸的代谢特征与其肝毒性的相关性[J]. 中国医学院杂志,2013,33(19):1611-1614.
    [13] Surendradoss J, Chang TKH, Abbott FS. Assessment of the role of in situ generated (E)-2, 4-diene-valproic acid in the toxicity of valproic acid and (E)-2-ene-valproic acid in sandwich-cultured rat hepatocytes[J]. Toxico Appl Pharm, 2012, 264(3):413-422.
    [14] Kiang TKL, Teng XW, Karagiozov S, et al. Role of oxidative metabolism in the effect of valproic acid on markers of cell viability, necrosis, and oxidative stress in sandwich-cultured rat hepatocytes[J]. Toxicol Sci, 2010, 118(2):501-509.
    [15] 刘爱旗,夏璐. CCK-8法与MTT法检测兔成纤维细胞活性的比较研究[J]. 中国医学创新,2013,10(2):12-13.
    [16] 陈海鹰,曹雨诞,颜晓静,等. 醋制降低京大戟对人正常肝细胞L02的毒性及机制研究[J].中国中药杂志,2013,38(6):866-870.
    [17] 王灿,马虹英,王方杰,等.丙戊酸肝毒性的早期预警及预防研究状况[J].中国临床药理学杂志,2015,31(2):150-154.
    [18] Abarikwu SO, Farombi EO, Pant AB. Biflavanone-kolaviron protects human dopaminergic SH-SY5Y cells against atrazine induced toxic insult[J]. Toxicol In Vitro, 2011, 25(4):848-858.
    [19] Lee MS, Lee YJ, Kim BJ, et al. The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid[J]. Arch Pharm Res, 2009, 32(7):1029-1035.
    [20] Chen ZJ,Wang XD,Wang HS,et al.Simultaneous determination of valproic and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epileosy[J]. Seizure,2012,21:110-117.
    [21] Gao S, Miao H, Tao X, et al. LC-MS/MS method for simultaneous determination of valproic acid and major metabolites in human plasma[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2011, 879(21):1939-1944.
  • 加载中
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索
Get Citation
PDF
XML

Article Metrics

Article views(3280) PDF downloads(806) Cited by()

Related
Proportional views

An in vitro study of hepatotoxicity induced by valproic acid and its metabolites

doi: 10.3969/j.issn.1006-0111.2017.01.011
  • 1. Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;College of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
  • 2. Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  • 3. College of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
  • Received Date: 2016-05-31
  • Rev Recd Date: 2016-09-29

Abstract: Objective To confirm the hepatotoxicity of valproic acid (VPA) and its metabolites(2-propyl-4-pentenoic acid, 3-hydroxy valproic acid, 5-hydroxy valproic acid) on human liver cells. Methods Cells were divided into control group and VPA-treated group. The control group was conventionally cultured while the VPA-treated group was treated with valproic acid and its metabolites. The rate of cell proliferation was assayed by CCK 8 protocol. The mRNA levels of CYP1A1, CYP1A2, PCNA, Bax and Bcl-2 were measured by real time PCR. The correlated protein levels were measured by Western Blotting. The activity of LDH, AST and ALT were also detected. Results Compared to the control group, with the increases of concentrations and reaction time of VPA and its metabolites, the proliferation rate of L02-cell was reduced, the mRNA and protein levels of CYP1A1, CYP1A2, and Bax was increased, the mRNA and protein level of PCNA and Bcl-2 was decreased, AST, ALT, and LDH were also elevated in the treated group. Conclusion Valproic acid and its metabolites were positively related to hepatotoxicity.

XIE Xinfang, WEN Yan, GAO Shouhong, YOU Chunhua, CHEN Wansheng, XIONG Xiaojuan. An in vitro study of hepatotoxicity induced by valproic acid and its metabolites[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(1): 43-47,53. doi: 10.3969/j.issn.1006-0111.2017.01.011
Citation: XIE Xinfang, WEN Yan, GAO Shouhong, YOU Chunhua, CHEN Wansheng, XIONG Xiaojuan. An in vitro study of hepatotoxicity induced by valproic acid and its metabolites[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(1): 43-47,53. doi: 10.3969/j.issn.1006-0111.2017.01.011
shu

    HTML

Reference (21)

Catalog

    版权所有：《药学实践与服务》编辑委员会

    Supervisor & Sponsors: Address: No 325 Guohe Road, ShanghaiPost Code: 200433

    Tel: （021）81871324,81871397 E-mail: yxsjzzs@163.com

    网站备案号 沪ICP备05003363号-1

    Supported by: Beijing Renhe Information Technology Co., Ltd.  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return