title: Effects of lovastatin treatment on the metabolic distributions in the Han:SPRD rat model of polycystic kidney disease.
abstract: BACKGROUND
  We previously demonstrated that lovastatin decreases cyst volume and improves kidney function in the Han:SPRD (Cy/+) rat model of ADPKD. Since endothelial dysfunction and inflammatory activity are evident in patients with ADPKD, we investigated whether lovastatin reduces the inflammation and vascular dysfunction and improves kidney cell energy metabolism of Cy/+ rats.
  
  
  METHODS
  Cy/+ and normal littermate control animals (+/+) were treated with either lovastatin (4 mg/kg/day) or vehicle (ethanol) from 3-8 weeks of age. 1H-NMR analysis was performed on water-soluble and lipid kidney fractions following perchloric acid extraction. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to assess endothelial dysfunction, oxidative stress and inflammation markers in plasma and kidney tissue extracts.
  
  
  RESULTS
  Cy/+ rats showed perturbations in fatty acid metabolism and increased synthesis of pro-inflammatory lipoxygenases-produced bioactive lipids was observed. Lovastatin decreased inflammatory markers, specifically 13-HODE, 12-HETE and leukotriene B4. In Cy/+ rats, lovastatin reduced the elevated homocysteine and allantoin plasma levels and increased arginine, that is known to positively affect NO production.
  
  
  CONCLUSIONS
  As previously described, lovastatin was able to decrease kidney weight and cyst volume density in Cy/+ rats. The decrease in cyst volume was accompanied by a reduction in arachidonic acid-mediated inflammation markers, the normalization of metabolism of NO precursors and the improvement of kidney energy cell metabolism.
authors.forename: Jelena
authors.initials: J
authors.lastname: Klawitter
authors.forename: Iram
authors.initials: I
authors.lastname: Zafar
authors.forename: Jost
authors.initials: J
authors.lastname: Klawitter
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Pennington
authors.forename: Jacek
authors.initials: J
authors.lastname: Klepacki
authors.forename: Berenice Y
authors.initials: BY
authors.lastname: Gitomer
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D008148:Lovastatin
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