Cholecalciferol pretreatment ameliorates ischemia/reperfusion-induced acute kidney injury through inhibiting ROS production, NF-KB pathway and pyroptosis

Acute kidney injury (AKI) is a common complication in patients with potentially life-threatening diseases, and it is also usually associated with unacceptable morbidity and mortality rates. Therefore, new and efficient therapies are urgently required to relieve AKI. It is well known that, reactive oxygen species (ROS), the NF-KB signaling pathways and pyroptosis are involved in AKI induced by ischemia/reperfusion (I/R). The present study seeks to further confirm the internal relationship between vitamin D deficiency and I/R-induced AKI in patients, and to explore the underlying mechanisms of ROS, NF-KB signaling pathways and pyroptosis in the renal ischemiareperfusion injury, as well as investigating the protective role of cholecalciferol. Patients with vitamin D deficiency show worse renal function reflected by postoperative glomerular filtration rate (GFR) and more release of proinflammatory cytokine IL-18 and IL-18. Renal cell injury and renal dysfunction induced by I/R surgery were attenuated in the ICR mice administered with cholecalciferol. Cholecalciferol reduced ROS production, suppressed activated NF-KB signaling, and inhibited gasdermin D (GSDMD, a pyroptosis execution protein)-mediated pyroptosis. Cholecalciferol therefore has potential, as a clinical drug, to protect renal function in I/R-induced AKI through reducing ROS production, NF-KB activation and GSDMD-mediated pyroptosis.

Automated summary

Acute kidney injury (AKI) is a common complication in patients with potentially life-threatening diseases, and vitamin D deficiency is found to be related to AKI induced by ischemia/reperfusion (I/R). This study shows that cholecalciferol can attenuate renal cell injury and dysfunction caused by I/R surgery through reducing ROS production, inhibiting NF-KB activation, and inhibiting GSDMD-mediated pyroptosis.