title: ATP-dependent potassium channels are implicated in simvastatin pretreatment-induced inhibition of apoptotic cell death after renal ischemia/reperfusion injury.
abstract: BACKGROUND
  Simvastatin is a widely used medication in cardiac care. Here we evaluate the role of ATP sensitive potassium (KATP) channels in simvastatin induced renal protection after renal ischemia/reperfusion (I/R) injury.
  
  
  METHODS
  A total of 81 male Wistar rats, were treated with simvastatin (10 and 20mg/kg/day; gavage, one week). Some groups received glibenclamide (KATP channel inhibitor; 5mg/kg) before ischemia (45min) and reperfusion (24h). Finally the kidneys were processed for histological analysis and measurement of biochemical parameters including tissue malondialdehyde (MDA), blood urea nitrogen (BUN), fractional excretion of sodium (FENa), creatinine clearance rate (CCr) and Bcl2-associated X protein (Bax) expression.
  
  
  RESULTS
  IR significantly increased serum Cr (p< 0.01) and BUN levels (p< 0.01), elevated FENa (p<0.01) and tissue MDA (p<0.01), and decreased CCr (p< 0.01) and induced histological damage. Bax pro-apoptotic protein was upregulated in renal tissue after I/R injury and downregulated in simvastatin pretreated group. Simvastatin at doses of 10 and 20mg/kg/day significantly reduced serum Cr and BUN levels (p< 0.05 vs. IR group), tissue MDA contents and FENa (p< 0.05 vs. I/R) and increased CCr (p< 0.05 vs. IR). Renal tissue injury was improved only in simvastatin 20mg/kg/day group (p< 0.05). Glibenclamide significantly abolished protective effects of simvastatin and increased serum Cr and BUN and FENa and decreased CCr (p< 0.05). It also abolished the effects of simvastatin on tissue injury and MDA contents and downregulated the Bax protein after IR injury (p< 0.05).
  
  
  CONCLUSIONS
  Opening of KATP channels is essential for simvastatin-induced renal protection against I/R injury.
authors.affiliation: Assistant Professor, Islamic Azad University, Najafabad Branch, Najafabad, Isfahan, Iran. kamdolat41@yahoo.com.
authors.forename: Kamran
authors.initials: K
authors.lastname: Dowlatshahi
authors.affiliation: Assistant Professor, National Nutrition and Food Technology Research Institute, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. nutritionist80@gmail.com.
authors.forename: Marjan
authors.initials: M
authors.lastname: Ajami
authors.affiliation: Assistant Professor, Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran. hrptoroudi@gmail.com.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Pazoki-Toroudi
authors.affiliation: Assistant Professor, Department of Cardiology, Iran University of Medical Sciences, Tehran, Iran. chancellor@iums.ac.ir.
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Hajimiresmaiel
keywords: Creatinine Clearance; Glibenclamide; KATP channels; Renal ischemia/reperfusion; Simvastatin