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10.12659/MSM.906362

http://scihub22266oqcxt.onion/10.12659/MSM.906362
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suck abstract from ncbi


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pmid29704392
      Med+Sci+Monit 2018 ; 24 (ä): 2620-2630
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  • The Nephroprotective Effect of MS-275 on Lipopolysaccharide (LPS)-Induced Acute Kidney Injury by Inhibiting Reactive Oxygen Species (ROS)-Oxidative Stress and Endoplasmic Reticulum Stress #MMPMID29704392
  • Zhang H ; Zhang W ; Jiao F ; Li X ; Zhang H ; Wang L ; Gong Z
  • Med Sci Monit 2018[Apr]; 24 (ä): 2620-2630 PMID29704392 show ga
  • BACKGROUND Histone deacetylase (HDAC) inhibitors can attenuate acute kidney injury (AKI)-mediated damage and reduce fibrosis in kidney disease models. The aim of the present study was to investigate the effects of the HDAC inhibitor MS-275 on lipopolysaccharide (LPS)-induced AKI and the associated mechanisms. MATERIAL AND METHODS A LPS-induced model in 6-8 weeks-old mice was established by intraperitoneal injection of LPS (10 mg/kg), with pre-treatment of MS-275 (2 mg/kg/day) administered intraperitoneally for five days. In addition, HK-2 cells were exposed to LPS (1 ?g/mL) at 0.1 nM, 1 nM, 10 nM, and 100 nM. For our in vitro MS-275 study, detection programs included histology, biochemical, immunohistochemistry, mRNA and protein expression as well as apoptosis. RESULTS MS-275 ameliorated renal damage, enhanced the survival rate of the LPS-induced sepsis model, decreased the expressions of TNF-?, IL-1?, IL-6, COX-2, and NF-?Bp65 nucleus translocation, suppressed the HDAC activity which was enhanced in septic AKI mice, and enhanced the acetylation of histone H3 and H4. Reactive oxygen species (ROS) production was enhanced in the kidney of LPS mice compared to control mice, while MS-275 suppressed the production of ROS in kidney tissue. In the in vitro studies, MS-275 reduced the LPS-induced apoptosis of HK-2 cells, inhibited ROS and MDA production, increased the production GSH and SOD activity, decreased the expressions of CHOP, GRP78, caspase3, and capase12, which was related to endoplasmic reticulum stress in LPS stimulated HK-2 cells. CONCLUSIONS MS-275 pre-treatment improved renal function and ameliorated histological alterations, inflammation, and ROS production in LPS-induced AKI mice and may act through inhibiting ROS-oxidative stress and endoplasmic reticulum stress.
  • |*Endoplasmic Reticulum Stress/drug effects [MESH]
  • |*Oxidative Stress/drug effects [MESH]
  • |Acetylation/drug effects [MESH]
  • |Acute Kidney Injury/*chemically induced/*drug therapy/pathology/physiopathology [MESH]
  • |Animals [MESH]
  • |Apoptosis/drug effects [MESH]
  • |Benzamides/pharmacology/*therapeutic use [MESH]
  • |Cell Line [MESH]
  • |Endoplasmic Reticulum Chaperone BiP [MESH]
  • |Histone Deacetylases/metabolism [MESH]
  • |Histones/metabolism [MESH]
  • |Humans [MESH]
  • |Inflammation Mediators/blood [MESH]
  • |Kidney/drug effects/*pathology/physiopathology [MESH]
  • |Lipopolysaccharides [MESH]
  • |Male [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Protective Agents/pharmacology/*therapeutic use [MESH]
  • |Pyridines/pharmacology/*therapeutic use [MESH]


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