PMID- 30659917
OWN - NLM
STAT- MEDLINE
DCOM- 20190807
LR  - 20190807
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Linking)
VI  - 85
DP  - 2019 Apr 1
TI  - Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney 
      injury by inhibiting the iNOS/NO signaling pathway in rats.
PG  - 1-9
LID - S1089-8603(18)30347-1 [pii]
LID - 10.1016/j.niox.2019.01.009 [doi]
AB  - Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses 
      multiple pharmacological actions. Herein, we explored the protective effect and 
      potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early 
      acute kidney injury (AKI) from the perspective of antioxidant stress. We found 
      that DEX (30 mug/kg, i.p.) ameliorated the renal dysfunction and histopathological 
      damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory 
      cells and cast formation) induced by LPS (10 mg/kg). DEX also attenuated renal 
      oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction 
      in production of reactive nitrogen species, decreasing malondialdehyde levels, as 
      well as increasing superoxide dismutase activity and glutathione content. DEX 
      prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa 
      B (IkappaB) and activation of nuclear factor kappa B (NF-kappaB) in LPS-induced early 
      AKI, as assessed by real-time quantitative polymerase chain reaction and protein 
      levels of c-Jun, c-Fos, IkappaB and NF-kappaB. Notably, DEX pretreatment had the same 
      effect as intraperitoneal injection of an inhibitor of inducible nitric oxide 
      synthase inhibitor (1400W; 15 mg/kg), and inhibited the activity of renal 
      inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA 
      and NO production. However, the protective effect of DEX on LPS-induced early AKI 
      was reversed by the alpha 2 adrenal receptor (alpha(2)-AR) inhibitor atipamezole, 
      whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX 
      protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO 
      signaling pathway, mainly by acting on alpha(2)-ARs instead of IRs.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Chen, Yongping
AU  - Chen Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Luan, Li
AU  - Luan L
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Wang, Chaoran
AU  - Wang C
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Song, Manyu
AU  - Song M
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Zhao, Yuan
AU  - Zhao Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Yao, Yujie
AU  - Yao Y
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Yang, Haotian
AU  - Yang H
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Ma, Biao
AU  - Ma B
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China.
FAU - Fan, Honggang
AU  - Fan H
AD  - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 
      150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and 
      Comparative Medicine, Northeast Agricultural University, Harbin, 150030, PR 
      China. Electronic address: fanhonggang2002@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190117
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 0 (Lipopolysaccharides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
MH  - Acute Kidney Injury/chemically induced/metabolism/*prevention & control
MH  - Adrenergic alpha-2 Receptor Agonists/chemistry/*pharmacology
MH  - Animals
MH  - Dexmedetomidine/chemistry/*pharmacology
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Nitric Oxide/*antagonists & inhibitors/metabolism
MH  - Nitric Oxide Synthase Type II/*antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
OTO - NOTNLM
OT  - AP-1/NF-kappaB
OT  - Acute kidney injury
OT  - Dexmedetomidine
OT  - Lipopolysaccharide
OT  - Oxidative stress
OT  - iNOS/NO
EDAT- 2019/01/20 06:00
MHDA- 2019/08/08 06:00
CRDT- 2019/01/20 06:00
PHST- 2018/11/13 00:00 [received]
PHST- 2019/01/09 00:00 [revised]
PHST- 2019/01/15 00:00 [accepted]
PHST- 2019/01/20 06:00 [pubmed]
PHST- 2019/08/08 06:00 [medline]
PHST- 2019/01/20 06:00 [entrez]
AID - S1089-8603(18)30347-1 [pii]
AID - 10.1016/j.niox.2019.01.009 [doi]
PST - ppublish
SO  - Nitric Oxide. 2019 Apr 1;85:1-9. doi: 10.1016/j.niox.2019.01.009. Epub 2019 Jan 
      17.