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

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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.

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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.

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  1. Magda Hamzawy and Sarah Ali Abdelhameed Gouda equal contributed to the work.

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Kasr El-Aini, Cairo University, AlSaray Street, Cairo, 11562, Egypt

    Magda Hamzawy, Sarah Ali Abdelhameed Gouda, Heba Shoukry & Nivin Sharawy

  2. Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt

    Laila Rashed

  3. Department of Histology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Mary Attia Morcos

  4. Cairo University Hospitals, Cairo, Egypt

    Nivin Sharawy

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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.

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Correspondence to Nivin Sharawy.

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Hamzawy, M., Gouda, S.A.A., Rashed, L. et al. 22-oxacalcitriol prevents acute kidney injury via inhibition of apoptosis and enhancement of autophagy. Clin Exp Nephrol 23, 43–55 (2019). https://doi.org/10.1007/s10157-018-1614-y

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