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Clinical and Experimental Nephrology

, Volume 23, Issue 1, pp 43–55 | Cite as

22-oxacalcitriol prevents acute kidney injury via inhibition of apoptosis and enhancement of autophagy

  • Magda Hamzawy
  • Sarah Ali Abdelhameed Gouda
  • Laila Rashed
  • Mary Attia Morcos
  • Heba Shoukry
  • Nivin SharawyEmail author
Original Article
  • 159 Downloads

Abstract

Background

The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between tubular cell damage and regeneration. Several lines of evidences suggest a potential renoprotective effect of vitamin D. In this study, we investigated the effect of 22-oxacalcitriol (OCT), a synthetic vitamin D analogue, on renal fate in a rat model of ischemia reperfusion injury (IRI) induced acute kidney injury (AKI).

Methods

22-oxacalcitriol (OCT) was administered via intraperitoneal (IP) injection before ischemia, and continued after IRI that was performed through bilateral clamping of the renal pedicles. 96 h after reperfusion, rats were sacrificed for the evaluation of autophagy, apoptosis, and cell cycle arrest. Additionally, assessments of toll-like receptors (TLR), interferon gamma (IFN-g) and sodium–hydrogen exchanger-1 (NHE-1) were also performed to examine their relations to OCT-mediated cell response.

Results

Treatment with OCT-attenuated functional deterioration and histological damage in IRI induced AKI, and significantly decreased cell apoptosis and fibrosis. In comparison with IRI rats, OCT + IRI rats manifested a significant exacerbation of autophagy as well as reduced cell cycle arrest. Moreover, the administration of OCT decreased IRI-induced upregulation of TLR4, IFN-g and NHE-1.

Conclusion

These results demonstrate that treatment with OCT has a renoprotective effect in ischemic AKI, possibly by suppressing cell loss. Changes in the expression of IFN-g and NHE-1 could partially link OCT to the cell survival-promoted effects.

Keywords

Acute kidney injury Ischemia reperfusion injury Vitamin D Autophagy Sodium–hydrogen exchanger Apoptosis 

Notes

Acknowledgements

The skillful technical assistance of Afaf, Aza and Tarek is appreciated. This work was supported by research Grants from the Faculty of Medicine, Cairo University.

Author contributions

MH, SAAG and NS carried out the study design and performed the analysis. LR, MAM and SAAG carried out studies recruitment and data extraction. NS, SAAG and MH participated in study qualifications. All authors helped to draft the manuscript.

Compliance with ethical standards

Conflict of interest

All the authors have declared no competing interest.

Supplementary material

10157_2018_1614_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 18 KB)

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Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Magda Hamzawy
    • 1
  • Sarah Ali Abdelhameed Gouda
    • 1
  • Laila Rashed
    • 2
  • Mary Attia Morcos
    • 3
  • Heba Shoukry
    • 1
  • Nivin Sharawy
    • 1
    • 4
    Email author
  1. 1.Department of Physiology, Faculty of MedicineKasr El-Aini, Cairo UniversityCairoEgypt
  2. 2.Department of Biochemistry, Faculty of MedicineCairo UniversityCairoEgypt
  3. 3.Department of Histology, Faculty of MedicineCairo UniversityCairoEgypt
  4. 4.Cairo University HospitalsCairoEgypt

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