Pretreatment with Cholecalciferol Alleviates Renal Cellular Stress Response during IschemiaReperfusion-Induced Acute Kidney Injury

Abstract EN

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 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-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 IRE1α and eIF2α 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.