PMID- 31243816
OWN - NLM
STAT- MEDLINE
DCOM- 20200914
LR  - 20200914
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 10
DP  - 2019 Oct
TI  - Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by 
      inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-kappaB 
      pathway.
PG  - 18509-18523
LID - 10.1002/jcb.29173 [doi]
AB  - Dexmedetomidine (DEX) prevents kidney damage caused by sepsis, but the mechanism 
      of this effect remains unclear. In this study, the protective molecular mechanism 
      of DEX in lipopolysaccharide (LPS)-induced acute kidney injury was investigated 
      and its potential pharmacological targets from the perspective of inhibiting 
      oxidative stress damage and the nucleotide-binding domain-like receptor protein 3 
      (NLRP3) inflammasome activation. Intraperitoneal injection of DEX (30 mug/kg) 
      significantly improved LPS (10 mg/kg) induced renal pathological damage and renal 
      dysfunction. DEX also ameliorated oxidative stress damage by reducing the 
      contents of reactive oxygen species, malondialdehyde and hydrogen peroxide, and 
      increasing the level of glutathione, as well as the activity of superoxide 
      dismutase and catalase. In addition, DEX prevented nuclear factor-kappa B (NF-kappaB) 
      activation and I-kappa B (IkappaB) phosphorylation, as well as the expressions of 
      NLRP3 inflammasome-associated protein and downstream IL-18 and IL-1beta. The 
      messengerRNA (mRNA) and protein expressions of toll-like receptor 4 (TLR4), NADPH 
      oxidase-4 (NOX4), NF-kappaB, and NLRP3 were also significantly reduced by DEX. Their 
      expressions were further evaluated by immunohistochemistry, yielding results were 
      consistent with the results of mRNA and protein detection. Interestingly, the 
      protective effects of DEX were reversed by atipamezole-an alpha 2 adrenal 
      receptor (alpha(2) AR) inhibitor, whereas idazoxan-an imidazoline receptor (IR) 
      inhibitor failed to reverse this change. In conclusion, DEX attenuated 
      LPS-induced AKI by inhibiting oxidative stress damage and NLRP3 inflammasome 
      activation via regulating the TLR4/NOX4/NF-kappaB pathway, mainly acting on the alpha(2) 
      AR rather than IR.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Yao, Yujie
AU  - Yao Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Hu, Xueyuan
AU  - Hu X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Feng, Xiujing
AU  - Feng X
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Zhao, Yuan
AU  - Zhao Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Song, Manyu
AU  - Song M
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Wang, Chaoran
AU  - Wang C
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
FAU - Fan, Honggang
AU  - Fan H
AUID- ORCID: 0000-0002-7671-6908
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
AD  - College of Veterinary Medicine, Heilongjiang Key Laboratory for Laboratory 
      Animals and Comparative Medicine, Harbin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190626
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Toll-Like Receptor 4)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (Nox4 protein, rat)
SB  - IM
MH  - Acute Kidney Injury/*chemically induced/*drug therapy
MH  - Animals
MH  - Blotting, Western
MH  - Dexmedetomidine/*therapeutic use
MH  - Immunohistochemistry
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - NADPH Oxidase 4/genetics/*metabolism
MH  - NF-kappa B/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 4/*metabolism
OTO - NOTNLM
OT  - LPS
OT  - NLRP3
OT  - acute kidney injury
OT  - dexmedetomidine
OT  - oxidative stress
OT  - rat
EDAT- 2019/06/28 06:00
MHDA- 2020/09/15 06:00
CRDT- 2019/06/28 06:00
PHST- 2019/04/17 00:00 [received]
PHST- 2019/05/22 00:00 [revised]
PHST- 2019/05/23 00:00 [accepted]
PHST- 2019/06/28 06:00 [pubmed]
PHST- 2020/09/15 06:00 [medline]
PHST- 2019/06/28 06:00 [entrez]
AID - 10.1002/jcb.29173 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Oct;120(10):18509-18523. doi: 10.1002/jcb.29173. Epub 2019 
      Jun 26.