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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 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.