title: Effect of chenodeoxycholic acid on fibrosis, inflammation and oxidative stress in kidney in high-fructose-fed Wistar rats.
abstract: BACKGROUND
  Recent studies indicate farnesoid X receptor (FXR) plays an important role in regulating lipid metabolism in kidney disease. The purpose of the present study is to investigate the effect of chenodeoxycholic acid (CDCA), a FXR agonist, on fibrosis, inflammation and oxidative stress in kidney in rats fed on high fructose.
  
  
  METHODS
  Twenty-four healthy male Wistar rats were randomly divided into three groups (n=8): normal control group, high fructose group and chenodeoxycholic acid group. Rats were sacrificed by the end of 16 weeks after feeding. Blood urea nitrogen, serum creatinine, fast glucose, lipid concentration were observed, spot urine samples were obtained to measure the albumin and creatinine levels. Triglyceride of renal cortices was detected. The mRNA level and protein contents of the fibrosis-inducing growth factor transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor (PAI-I), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), oxidative stress index NADPH oxidase 2 (Nox2) and p22phox in kidney were examined. The pathological changes of kidney were examined by PAS staining and immunohistochemical staining. Electron microscope sections were made to measure glomerular basement membrane (GBM) width.
  
  
  RESULTS
  Renal injuries including mesangial expansion, GBM thickness and podocyte foot process effacement were found in fructose-fed Wistar rats, FXR agonist CDCA modulates renal lipid metabolism, decreases proteinuria and improves renal fibrosis, inflammation and oxidation stress. High-fructose-feeding may cause lipid nephrotoxicity through down-regulated farnesoid X receptor and increases expression of profibrotic growth factors, proinflammatory cytokines, and oxidative stress in Wistar rats.
  
  
  CONCLUSIONS
  FXR activation by chenodeoxycholic acid can prevent the injury in kidney induced by high fructose feeding.
authors.affiliation: Internal medicine department of Hebei Medical University Shijiazhuang, Hebei, PR China.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Hu
authors.forename: Luping
authors.initials: L
authors.lastname: Ren
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Guangyao
authors.initials: G
authors.lastname: Song
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D005355:Fibrosis; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009393:Nephritis / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D015415:Biomarkers; D002635:Chenodeoxycholic Acid; D016207:Cytokines; D004040:Dietary Carbohydrates; D005632:Fructose; D008562:Membrane Glycoproteins; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D017395:Plasminogen Activator Inhibitor 1; D018160:Receptors, Cytoplasmic and Nuclear; D053773:Transforming Growth Factor beta1; D000099150:Receptor, Farnesoid X-Activated; C500593:Cybb protein, rat; C515768:Cyba protein, rat