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

• Published in: Clinical and experimental nephrology Vol. 23; no. 1; pp. 43 - 55
• Main Authors: Hamzawy, Magda, Gouda, Sarah Ali Abdelhameed, Rashed, Laila, Morcos, Mary Attia, Shoukry, Heba, Sharawy, Nivin
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.01.2019; Springer Nature B.V
• Subjects: Apoptosis; Autophagy; Cell cycle; Cell survival; Fibrosis; Ischemia; Kidneys; Medicine; Medicine & Public Health; Na+/H+-exchanging ATPase; Nephrology; Original Article; Phagocytosis; Reperfusion; Rodents; Sodium; TLR4 protein; Toll-like receptors; Urology; Vitamin D; Ischemia reperfusion injury; Vitamin D; Autophagy; Acute kidney injury; Sodium–hydrogen exchanger; Apoptosis
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-018-1614-y

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.