title: An effective assessment of valproate sodium-induced hepatotoxicity with UPLC-MS and (1)HNMR-based metabonomics approach.
abstract: Valproate sodium is one of the most prescribed antiepileptic drugs. However, valproate sodium has various side effects, especially its toxicity on liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods for toxicity evaluation are desired. To evaluate the toxicity of valproate sodium on liver, we performed both UPLC-MS and (1)HNMR-based metabonomics analysis of serum samples from 34 epileptic patients (age: 42.0±18.6, 18 male/16 female) after valproate sodium treatment. Compared to conventional markers, the serum metabolic profiles provided clear distinction of the valproate sodium induced normal liver function and abnormal liver function in epileptic patients. Through multivariate statistical analysis, we identified marker metabolites associated with the hepatotoxicity induced by valproate sodium, such as glucose, lactate, acetoacetate, VLDL/LDL, lysophosphatidylcholines, phosphatidylcholines, choline, creatine, amino acids, N-acetyl glycoprotein, pyruvate and uric acid. This metabonomics approach may provide effective way to evaluate the valproate sodium-induced toxicity in a manner that can complement current measures. This approach is expected to find broader application in other drug-induced toxicity assessment.
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110001, PR China.
authors.forename: Taoguang
authors.initials: T
authors.lastname: Huo
authors.affiliation: The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China; School of Pharmacy, China Medical University, Shenyang 110001, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Lu
authors.affiliation: The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China; School of Pharmacy, China Medical University, Shenyang 110001, PR China.
authors.forename: Lianyue
authors.initials: L
authors.lastname: Qu
authors.affiliation: The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China; School of Pharmacy, China Medical University, Shenyang 110001, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China; School of Pharmacy, China Medical University, Shenyang 110001, PR China. Electronic address: caishuang1972@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D014635:Valproic Acid / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: (1)HNMR; Hepatotoxicity; Metabonomics; UPLC–MS; Valproate sodium