title: Pretreatment with nebivolol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischaemia-reperfusion injury.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischaemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischaemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a β1-adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI.
  
  
  METHODS
  Twenty Wistar albino rats were divided into three groups: sham-operated , ischaemia-reperfusion, and nebivolol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 min followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy.
  
  
  RESULTS
  Creatinine levels increased significantly in the ischaemia-reperfusion group compared to the sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group.
  
  
  CONCLUSIONS
  Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.
authors.affiliation: Department of Nephrology, Izmir Tepecik Research and Training Hospital, Izmir, Turkey.
authors.forename: Sibel
authors.initials: S
authors.lastname: Ersan
authors.affiliation: Department of Nephrology, Izmir Tepecik Research and Training Hospital, Izmir, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tanrısev
authors.affiliation: Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University Hospital, Izmir, Turkey.
authors.forename: Zahide
authors.initials: Z
authors.lastname: Cavdar
authors.affiliation: Department of Laboratory Animal Sciences, Dokuz Eylul University Hospital, Izmir, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Celık
authors.affiliation: Department of Pathology, Dokuz Eylul University Hospital, Izmir, Turkey.
authors.forename: Mehtat
authors.initials: M
authors.lastname: Unlu
authors.affiliation: Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University Hospital, Izmir, Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Kocak
authors.affiliation: Department of Bioistatistics, Ege University Hospital, Izmir, Turkey.
authors.forename: Timur
authors.initials: T
authors.lastname: Kose
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D000068577:Nebivolol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000068577:Nebivolol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: acute kidney injury; acute tubular necrosis; ischaemia reperfusion; matrix metalloproteinases; nebivolol