Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats

Azak, Alper; Huddam, Bülent; Haberal, Nihan; Koçak, Gülgün; Ortabozkoyun, Levent; Şeneş, Mehmet; Akdoğan, MF; Denizli, Nazım; Duranay, Murat

doi:10.1308/003588413x13629960049117

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…Quite few of them have explored the effect of VDR in clinical AKI or in vivo models. Azak A et al has reported that VDR activator paricalcitol could mitigate renal ischemia/reperfusion injury in rats 22 . Our quite recent work also showed a promising protection of vitamin D-VDR signaling against apoptosis in an AKI model induced by LPS 23 .…”

Section: Discussionmentioning

confidence: 99%

VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis

et al. 2020

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Our preliminary work has revealed that vitamin D receptor (VDR) activation is protective against cisplatin induced acute kidney injury (AKI). Ferroptosis was recently reported to be involved in AKI. Here in this study, we investigated the internal relation between ferroptosis and the protective effect of VDR in cisplatin induced AKI. By using ferroptosis inhibitor ferrostatin-1 and measurement of ferroptotic cell death phenotype in both in vivo and in vitro cisplatin induced AKI model, we observed the decreased blood urea nitrogen, creatinine, and tissue injury by ferrostatin-1, hence validated the essential involvement of ferroptosis in cisplatin induced AKI. VDR agonist paricalcitol could both functionally and histologically attenuate cisplatin induced AKI by decreasing lipid peroxidation (featured phenotype of ferroptosis), biomarker 4-hydroxynonenal (4HNE), and malondialdehyde (MDA), while reversing glutathione peroxidase 4 (GPX4, key regulator of ferroptosis) downregulation. VDR knockout mouse exhibited much more ferroptotic cell death and worsen kidney injury than wild type mice. And VDR deficiency remarkably decreased the expression of GPX4 under cisplatin stress in both in vivo and in vitro, further luciferase reporter gene assay showed that GPX4 were target gene of transcription factor VDR. In addition, in vitro study showed that GPX4 inhibition by siRNA largely abolished the protective effect of paricalcitol against cisplatin induced tubular cell injury. Besides, pretreatment of paricalcitol could also alleviated Erastin (an inducer of ferroptosis) induced cell death in HK-2 cell. These data suggested that ferroptosis plays an important role in cisplatin induced AKI. VDR activation can protect against cisplatin induced renal injury by inhibiting ferroptosis partly via trans-regulation of GPX4.

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Section: Discussionmentioning

confidence: 99%

VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis

et al. 2020

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“…Beyond their role in maintaining calcium and phosphate homeostasis, vitamin D metabolites influence the expression of more than 200 target genes, 19 including genes that affect a variety of critical immunomodulatory pathways relevant to AKI. 125,126 In animal models, pre-administration of 1,25D attenuated AKI resulting from a variety of nephrotoxic insults, including ischemia-reperfusion injury, [127][128][129] gentamicin, 130 cyclosporine, 131 cisplatin, 132 glomerulonephritis, 133 and obstruction. 134 Furthermore, de Braganca et al 135 investigated the effects of dietary-induced 25D deficiency on the severity of AKI in rats.…”

Section: Vitamin D Metabolites As Novel Therapies In Aki and Criticalmentioning

confidence: 99%

Dysregulated Mineral Metabolism in AKI

Leaf

Christov

2019

Seminars in Nephrology

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Dysregulated mineral metabolism is a nearly universal sequalae of acute kidney injury (AKI). Abnormalities in circulating mineral metabolites observed in patients with AKI include hypocalcemia, hyperparathyroidism, hyperphosphatemia, decreased vitamin D metabolite levels, and increased fibroblast growth factor 23 levels. We review the pathophysiology of dysregulated mineral metabolism in AKI with a focus on calcium, phosphate, parathyroid hormone, and vitamin D metabolites. We discuss how mineral metabolite levels can serve as novel prognostic markers for incident AKI and other related outcomes in various clinical settings. Finally, we discuss how vitamin D metabolites potentially could be used as novel therapeutic agents for AKI prevention and treatment.

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“…assessed the relationship between serum vitamin D levels and the prognosis of AKI and showed that the degree of 1,25 (OH) 2 D 3 deficiency is associated with the severity of AKI [ 74 ]. Ischemia/reperfusion (IR) is an important pathogenic factor for AKI, and it has been shown that therapy with the VDR activator paricalcitol can attenuate renal IR injury by improving tubular necrosis and medullar congestion [ 75 ]. Furthermore, Gonçalves et al .…”

Section: Vdr In Secondary Kidney Diseasesmentioning

confidence: 99%

Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases

Yang

Wang

et al. 2018

CMC

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Background: Kidney disease is a serious problem that adversely affects human health, but critical knowledge is lacking on how to effectively treat established chronic kidney disease. Mounting evidence from animal and clinical studies has suggested that Vitamin D Re-ceptor (VDR) activation has beneficial effects on various renal diseases.Methods: A structured search of published research literature regarding VDR structure and function, VDR in various renal diseases (e.g., IgA nephropathy, idiopathic nephrotic syndrome, renal cell carcinoma, diabetic nephropathy, lupus nephritis) and therapies targeting VDR was performed for several databases.Result: Included in this study are the results from 177 published research articles. Evidence from these papers indicates that VDR activation is involved in the protection against renal inju-ry in kidney diseases by a variety of mechanisms, including suppression of RAS activation, an-ti-inflammation, inhibiting renal fibrogenesis, restoring mitochondrial function, suppression of autoimmunity and renal cell apoptosis.Conclusion: VDR offers an attractive druggable target for renal diseases. Increasing our under-standing of VDR in the kidney is a fertile area of research and may provide effective weapons in the fight against kidney diseases

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Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats

Abstract: Paricalcitol therapy improved renal I/R injury in terms of serum and histopathological parameters. These potential beneficial effects need to be further investigated.

Cited by 15 publications

References 25 publications

VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis

VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis

Dysregulated Mineral Metabolism in AKI

Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases

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