Medical Journal of the Islamic Republic Of Iran

en ATP-dependent potassium channels are implicated in simvastatin pretreatment-induced inhibition of apoptotic cell death after renal ischemia/reperfusion injury Physiology Physiology Original Research Original Research   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).    Conclusion: Opening of KATP channels is essential for simvastatin-induced renal protection against I/R injury.   Creatinine Clearance, KATP channels, Renal ischemia/reperfusion, Simvastatin, Glibenclamide. 263 272 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-1-806&slc_lang=en&sid=1 Kamran Dowlatshahi kamdolat41@yahoo.com 200319475328460024436 200319475328460024436 No Islamic Azad University, Najafabad Branch, Najafabad, Isfahan, Iran. Marjan Ajami nutritionist80@gmail.com 200319475328460024437 200319475328460024437 No National Nutrition and Food Technology Research Institute, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Hamidreza Pazoki-Toroudi hrptoroudi@gmail.com 200319475328460024438 200319475328460024438 No Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran. Seyed Javad Hajimiresmaiel chancellor@iums.ac.ir 200319475328460024439 200319475328460024439 Yes Department of Cardiology, Iran University of Medical Sciences, Tehran, Iran.