title: Toxicogenomic analysis of the gene expression changes in rat liver after a 28-day oral Tripterygium wilfordii multiglycoside exposure.
abstract: BACKGROUND
  Tripterygium wilfordii multiglycoside (GTW), which is an extract derived from Tripterygium wilfordii Hook.f., has been used for the treatment of rheumatoid arthritis and other immune diseases in China. However, its potential hepatotoxicity has not been completely investigated.
  
  
  OBJECTIVE
  The aim of the study was to determine the hepatotoxicity of GTW in Wistar rats and to investigate the underlying cellular mechanism further by microarray analysis.
  
  
  METHODS
  Doses of GTW at 60, 100 and 120mg/kg/day were administered by oral gavage for subchronic toxicity in Wistar rats. Changes in the hepatic gene expression were identified with oligonucleotide microarrays at the 100-mg/kg/day dose level to study the hepatotoxic mechanism of GTW.
  
  
  CONCLUSIONS
  A number of changes in the body weight and food consumption, absolute and relative liver weight, biochemical analysis and histopathology were observed after the subacute exposure to GTW, and a dose-dependent hepatotoxicity was observed. A total of 1312 genes were found to be significantly altered (2-fold, P<0.05), including 582 up-regulated genes and 730 down-regulated genes. According to our biological pathway analysis, the GTW resulted in aberrant gene expression in metabolic pathways and the peroxisome proliferator-activated receptor (PPAR) signaling pathway and cellular stress. Real-time PCR analyses of several genes verified these results. Consequently, our gene expression microarray study will be useful for future GTW hepatotoxicity studies.
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yurong
authors.initials: Y
authors.lastname: Wang
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000302:isolation & purification / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000008:administration & dosage* / Q000302:isolation & purification / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects / Q000235:genetics; D008517:Phytotherapy; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D059550:Toxicity Tests, Subchronic; D043922:Toxicogenetics / Q000379:methods; D029757:Tripterygium / Q000737:chemistry
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D006027:Glycosides; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; C508235:multiglycosidorum tripterygii