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 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.
Highlights
Acute kidney injury (AKI), defined as a rapid renal dysfunction with severe tubular damage, is a global public health concern associated with high morbidity, mortality, and healthcare costs [1,2,3,4]
Two recent reports found that pretreatment with cholecalciferol protected against sepsis-induced acute kidney injury (AKI) in mice [23, 29]
Additional study showed that pretreatment with cholecalciferol protected against I/R-induced hepatic injury in rats [30]
Summary
Acute kidney injury (AKI), defined as a rapid renal dysfunction with severe tubular damage, is a global public health concern associated with high morbidity, mortality, and healthcare costs [1,2,3,4]. According to a recent report, oxidative stress played important roles during I/R-evoked AKI [7]. Several studies found that renal endoplasmic reticulum (ER) stress was involved in the pathogenesis of I/R-evoked AKI [8,9,10]. 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. Renal cellular stress and kidney injury were measured at different time points after reperfusion. I/R-induced AKI was alleviated in mice pretreated with cholecalciferol. I/R-induced upregulation of heme oxygenase- (HO-) 1, gshpx and gshrd, was attenuated in mice pretreated with cholecalciferol. Pretreatment with cholecalciferol protects against I/R-induced AKI partially through suppressing renal cellular stress response
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