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-) 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 Chol + I/R group, mice were orally administered with three doses of cholecalciferol (25 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 and eIF2 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 , , and , was inhibited by cholecalciferol. I/R-induced upregulation of heme oxygenase- (HO-) 1, and , was attenuated in mice pretreated with cholecalciferol.

Conclusions: Pretreatment with cholecalciferol protects against I/R-induced AKI partially through suppressing renal cellular stress response.