title: Hyperoxaluria-induced tubular ischemia: the effect of verapamil on the limitation of tissue HIF-1 alpha levels in renal parenchyma.
abstract: OBJECTIVE
  The effect of verapamil on tubular ischemia that is demonstrated by HIF-1alpha positivity in tubular cells following hyperoxaluria was evaluated in a rabbit model.
  
  
  METHODS
  Thirty-six healthy male rabbits were randomly divided into three groups. Animals in the hyperoxaluric group were fed with 0.75% ethylene glycol. The verapamil group was fed identically to the hyperoxaluric group. Additionally, the verapamil group received verapamil orally (0.1 mg/kg). The control group received no special diet. Six animals in each group were killed on the 7th day of the experiment and the remaining six at the 28th day. Kidneys of the rabbits were examined by histopathologic and immunohistochemical analysis to detect the presence and degree of HIF-1alpha positivity.
  
  
  RESULTS
  On the 7th day analysis, severe and moderate degree staining for HIF-1alpha in hyperoxaluric group were shown in four and two, respectively. In the verapamil group, however, three of six specimens showed nuclear staining (moderate in two and severe in one). Two of six specimens in the control group had minimal staining. The 28th day evaluation showed that two of the hyperoxaluric group had minimal degree nuclear staining but not in the remaining four. No staining was shown in the verapamil and control group animals.
  
  
  CONCLUSIONS
  Hyperoxaluria-related ischemia formation may be responsible for subsequent alterations in renal tubules. As a protective agent, verapamil was found to limit the presence of hypoxic changes as documented by HIF-1 alpha positivity in this study. These data also support the presence ischemic insult after hyperoxaluria induction in animal model.
authors.affiliation: Department of Urology, Yeditepe University Medical Faculty, Yeditepe University Hospital, Devlet yolu, Ankara cad. 102/104, Kozyatagi, 34752 Istanbul, Turkey. fyencilek@yeditepe.edu.tr
authors.forename: Faruk
authors.initials: F
authors.lastname: Yencilek
authors.forename: Kemal
authors.initials: K
authors.lastname: Sarica
authors.forename: Bilal
authors.initials: B
authors.lastname: Eryildirim
authors.forename: Sakip
authors.initials: S
authors.lastname: Erturhan
authors.forename: Metin
authors.initials: M
authors.lastname: Karakok
authors.forename: Ugur
authors.initials: U
authors.lastname: Kuyumcuoglu
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006959:Hyperoxaluria / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007511:Ischemia / Q000209:etiology* / Q000517:prevention & control*; D007668:Kidney / Q000737:chemistry; D007684:Kidney Tubules / Q000098:blood supply* / Q000737:chemistry*; D008297:Male; D011817:Rabbits; D013997:Time Factors; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D002121:Calcium Channel Blockers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014700:Verapamil