Pretreatment with Cholecalciferol Alleviates Renal Cellular Stress Response during Ischemia/Reperfusion-Induced Acute Kidney Injury

Abstract

Background . Cellular stress is involved in ischemia/reperfusion- (I/R-) induced acute kidney injury (AKI). This study is aimed at investigating the effects of pretreatment with cholecalciferol on renal oxidative stress and endoplasmic reticulum (ER) stress during I/R-induced AKI. Methods . I/R-induced AKI was established by cross-clamping renal pedicles for 90 minutes and then reperfusion. In the<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mtext>Chol</mml:mtext><mml:mo>+</mml:mo><mml:mtext>I</mml:mtext><mml:mo>/</mml:mo><mml:mtext>R</mml:mtext></mml:math>group, mice were orally administered with three doses of cholecalciferol (25 μ g/kg) at 1, 24, and 48 h before ischemia. Renal cellular stress and kidney injury were measured at different time points after reperfusion. Results . I/R-induced AKI was alleviated in mice pretreated with cholecalciferol. In addition, I/R-induced renal cell apoptosis, as determined by TUNEL, was suppressed by cholecalciferol. Additional experiment showed that I/R-induced upregulation of renal GRP78 and CHOP was inhibited by cholecalciferol. I/R-induced renal IRE1 α and eIF2 α phosphorylation was attenuated by cholecalciferol. Moreover, I/R-induced renal GSH depletion, lipid peroxidation, and protein nitration were blocked in mice pretreated with cholecalciferol. I/R-induced upregulation of renal NADPH oxidases, such as p47phox , gp91phox , and nox4 , was inhibited by cholecalciferol. I/R-induced upregulation of heme oxygenase- (HO-) 1, gshpx and gshrd , was attenuated in mice pretreated with cholecalciferol. Conclusions . Pretreatment with cholecalciferol protects against I/R-induced AKI partially through suppressing renal cellular stress response.