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

Background. Cellular stress is involved in ischemia/reperfusion- (I/R-) inducedacute kidney injury (AKI). This study is aimed at investigating the effects of pretreatment with cholecalciferolon renal oxidative stress and endoplasmic reticulum (ER) stress during I/R- inducedAKI. Methods. I/R- inducedAKI was established by cross-clamping renal pedicles for 90 minutes and then reperfusion. In the group, mice were orally administered with three doses of cholecalciferol(25 μg/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- inducedAKI was alleviated in mice pretreated with cholecalciferol. In addition, I/R- inducedrenal cell apoptosis, as determined by TUNEL, was suppressed by cholecalciferol. Additional experiment showed that I/R- inducedupregulation of renal GRP78 and CHOP was inhibited by cholecalciferol. I/R- inducedrenal IRE1α and eIF2α phosphorylation was attenuated by cholecalciferol. Moreover, I/R- inducedrenal GSH depletion, lipid peroxidation, and protein nitration were blocked in mice pretreated with cholecalciferol. I/R- inducedupregulation of renal NADPH oxidases, such as p47phox, gp91phox, and nox4, was inhibited by cholecalciferol. I/R- inducedupregulation of heme oxygenase- (HO-) 1, gshpx and gshrd, was attenuated in mice pretreated with cholecalciferol. Conclusions. Pretreatment with cholecalciferolprotects against I/R- inducedAKI partially through suppressing renal cellular stress response.