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10.1016/j.bbrc.2014.01.005

http://scihub22266oqcxt.onion/10.1016/j.bbrc.2014.01.005
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24434153!ä!24434153

suck abstract from ncbi


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pmid24434153      Biochem+Biophys+Res+Commun 2014 ; 444 (2): 121-7
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  • Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-kappaB pathway in ischemia/reperfusion-induced acute kidney injury #MMPMID24434153
  • Lee JW; Kim SC; Ko YS; Lee HY; Cho E; Kim MG; Jo SK; Cho WY; Kim HK
  • Biochem Biophys Res Commun 2014[Feb]; 444 (2): 121-7 PMID24434153show ga
  • BACKGROUND: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI). METHODS: Paricalcitol was administered via intraperitoneal (IP) injection at 24h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells. RESULTS: Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-kappaB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-alpha-induced depletion of cytosolic IkappaB in HK-2 cells. CONCLUSION: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-kappaB mediated inflammation.
  • |Acute Kidney Injury/blood/etiology/*metabolism[MESH]
  • |Animals[MESH]
  • |Blotting, Western[MESH]
  • |Cell Line[MESH]
  • |Chemokine CCL2/metabolism[MESH]
  • |Chemokines/metabolism[MESH]
  • |Creatine/blood[MESH]
  • |Ergocalciferols/*pharmacology[MESH]
  • |Humans[MESH]
  • |I-kappa B Kinase/metabolism[MESH]
  • |Inflammation/blood/etiology/metabolism[MESH]
  • |Interleukin-6/metabolism[MESH]
  • |Kidney/drug effects/metabolism/pathology[MESH]
  • |Macrophages/metabolism/pathology[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Neutrophils/metabolism/pathology[MESH]
  • |Reperfusion Injury/complications[MESH]
  • |Signal Transduction/*drug effects[MESH]
  • |Toll-Like Receptor 4/*metabolism[MESH]


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