title: Dexamethasone decreases cholestatic liver injury via inhibition of intrinsic pathway with simultaneous enhancement of mitochondrial biogenesis.
abstract: BACKGROUND
  Mitochondria are known to be involved in cholestatic liver injury. We tested the hypothesis that glucocorticoids can modulate mitochondrial function to alleviate cholestatic liver injury.
  
  
  METHODS
  A rat model of cholestasis was established by bile duct ligation (BDL), with a sham group receiving laparotomy without BDL, and a group receiving dexamethasone (DEX) treatment after BDL.
  
  
  RESULTS
  The liver function including total bilirubin levels, alanine transaminase and aspartate transaminase activities was significantly improved in the DEX treatment group in comparison to the BDL group. There was a significant upregulation of liver peroxisome proliferator-activated receptor γ coactivator-1α and mitochondrial transcriptional factor A protein between 6 and 72 h was found in the DEX group. DEX treatment significantly down-regulated Bax, caspase 9 and caspase 3 expression induced by BDL at 24-72 h, but had little effect on the expression of caspase 8, Bcl(2,) Fas and Fas-FasL complex. Consequently, the number of apoptotic liver cells in the DEX group was significantly less than in the BDL group at 72 h.
  
  
  CONCLUSIONS
  Our results indicate that glucocorticoids decreases cholestatic liver injury within hours after BDL. Early glucocorticoids treatment can enhance the mitochondrial biogenesis and modulate the intrinsic but not extrinsic pathway of apoptosis following BDL.
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Jin-Bor
authors.initials: JB
authors.lastname: Chen
authors.forename: Cha-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Chao-Chen
authors.initials: CC
authors.lastname: Huang
authors.forename: Yao-Min
authors.initials: YM
authors.lastname: Chou
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Huang
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001652:Bile Ducts / Q000601:surgery; D002779:Cholestasis / Q000150:complications*; D004272:DNA, Mitochondrial / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D018628:Gene Dosage / Q000235:genetics; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D005938:Glucocorticoids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; C489030:Tfam protein, rat; D014157:Transcription Factors; D003907:Dexamethasone