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

Abstract

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-κB 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-κB signaling pathways and pyroptosis in the renal ischemia-reperfusion 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-1β 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-κB 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-κB activation and GSDMD-mediated pyroptosis.

• Authors: Wangyu Wu, Dongyan Liu, Yuxiang Zhao, Taotao Zhang, Jiaxing Ma, Dengdian Wang, Jun Li, Weiwei Qian, Zhihui Zhang, Dexin Yu, Tao Zhang
• Journal: Acta histochemica (Acta Histochem) Vol. 124 Issue 4 Pg. 151875 (May 2022) ISSN: 1618-0372 [Electronic] Germany
• PMID: 35334282 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier GmbH.

Chemical References

• NF-kappa B
• Reactive Oxygen Species
• Cholecalciferol

Topics

• Acute Kidney Injury (drug therapy)
• Animals
• Cholecalciferol (pharmacology)
• Humans
• Ischemia
• Kidney (metabolism)
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Pyroptosis (physiology)
• Reactive Oxygen Species (metabolism)
• Reperfusion
• Reperfusion Injury (drug therapy, metabolism)
• Vitamin D Deficiency