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 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.

Metabolomics Analysis of Hippocampus and Cortex in a Rat Model of Traumatic Brain Injury in the Subacute Phase

“…The consequences of TBI cause changes of neuronal function, especially in the cortex ( Carron et al, 2016 ). Increased cholecalciferol is observed in brain tissues, which is associated with the regulation of calcium homeostasis ( Bivona et al, 2018 ), restoration of autophagy flux ( Campbell and Spector, 2012 ; Cui et al, 2017 ), and decrease in apoptosis ( Li et al, 2019 ; Molinari et al, 2019 ). Our results also show increased cholecalciferol in the cortex of subacute TBI, which is related to neuroprotection exertion ( Mechanick et al, 1997 ; Van de Kerkhof et al, 2002 ).…”

TUNEL Assay: A Powerful Tool for Kidney Injury Evaluation

“…After cold ischemia, TUNEL-positive cells were usually observed within 2–24 h during reperfusion [ 90 ], or more narrowly, between 14 and 17 h after ischemia [ 91 ], and sometimes were still observed as late as 7 days in transplant rejection [ 92 ]. Similarly, in ischemia-reperfusion models, TUNEL-positive cells were most often observed 24 h after reperfusion [ 44 , 93 , 94 ], or within the range between 4 [ 95 , 96 ] and 72 h [ 97 ]. In both transplantation and ischemic AKI studies, TUNEL-positive cells were localized to distal and proximal tubular epithelial cells [ 44 , 93 ].…”

New insights into the pathophysiological mechanisms underlying cardiorenal syndrome

“…heart failure) [46,47]. Cardiorenal "connectors" such as erythrocyte superoxide dismutase (SOD1), GSH, and NADPH have also been used to measure kidney and heart injury [48][49][50][51][52][53].…”