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

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

  • Acta Histochem. 2022 May;124(4):151875. doi: 10.1016/j.acthis.2022.151875.
Wangyu Wu 1 Dongyan Liu 2 Yuxiang Zhao 1 Taotao Zhang 1 Jiaxing Ma 1 Dengdian Wang 1 Jun Li 1 Weiwei Qian 1 Zhihui Zhang 1 Dexin Yu 1 Tao Zhang 3
Affiliations

Affiliations

  • 1 Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
  • 2 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health & Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China; University of Science and Technology of China, Hefei 230026, China.
  • 3 Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China. Electronic address: zhangtao@ahmu.edu.cn.
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.

Keywords

Acute kidney injury; Cholecalciferol; Ischemia and reperfusion; NF-κB pathway; Pyroptosis; ROS.

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