PMID- 33211285
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20211129
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 39
IP  - 3
DP  - 2021 Jun
TI  - The Protective Effects of Ramelteon Against Isoflurane-Induced Insults and 
      Inflammatory Response in Brain Microvascular Endothelial Cells.
PG  - 677-686
LID - 10.1007/s12640-020-00309-7 [doi]
AB  - Anesthetic-induced cognitive impairment has been observed clinically. The 
      mechanism underlying anesthetic-induced cognitive impairment is closely 
      associated with neuronal apoptosis and neuroinflammation. Ramelteon is a potent 
      and highly selective melatonin receptor agonist that has been used for the 
      treatment of insomnia and has been reported to have an anti-inflammatory effect. 
      In this study, we aimed to investigate the protective effects of Ramelteon 
      against the cytotoxicity induced by isoflurane in brain microvascular endothelial 
      cells. Our results show that Ramelteon ameliorated oxidative stress by 
      suppressing the generation of mitochondrial reactive oxygen species (ROS) in 
      human brain microvascular endothelial cells (HBMVECs). In addition, Ramelteon 
      displayed a robust anti-inflammatory capacity against isoflurane-induced insults 
      and inflammation by reducing the generation of interleukin-1beta (IL-1beta), 
      transforming growth factor-beta (TGF-beta), monocyte chemotactic protein 1 (MCP-1), 
      stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), and 
      MMP-9. Furthermore, Ramelteon reduced the expression of cell adhesion molecules 
      such as intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Importantly, 
      Ramelteon downregulated the activation of the p38MAPK/NF-kappaB signaling pathway, 
      which is the key transcriptional regulator in the inflammation process. Our 
      findings in the present study provide new evidence for the use of Ramelteon in 
      the prevention of isoflurane-induced insults in brain endothelial cells.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical 
      University, 368 Yehai Av., Longhua District, Haikou, 570311, Hainan, China. 
      wangtao567@163.com.
FAU - Li, Zhen
AU  - Li Z
AD  - Department of Anesthesiology, Qinghai Women's and Children's Hospital, Xi'ning, 
      China.
FAU - Xia, Shuyun
AU  - Xia S
AD  - Department of Respiratory Medicine, Pingdu People's Hospital, Pingdu, China.
FAU - Xu, Zhixin
AU  - Xu Z
AD  - Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical 
      University, 368 Yehai Av., Longhua District, Haikou, 570311, Hainan, China.
FAU - Chen, Xiaofang
AU  - Chen X
AD  - Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical 
      University, 368 Yehai Av., Longhua District, Haikou, 570311, Hainan, China.
FAU - Sun, Hu
AU  - Sun H
AD  - Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical 
      University, 368 Yehai Av., Longhua District, Haikou, 570311, Hainan, China.
LA  - eng
PT  - Journal Article
DEP - 20201119
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Indenes)
RN  - 0 (Inflammation Mediators)
RN  - 901AS54I69 (ramelteon)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Anesthetics, Inhalation/toxicity
MH  - Brain/cytology/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Indenes/*pharmacology
MH  - Inflammation Mediators/*antagonists & inhibitors/metabolism
MH  - Isoflurane/*toxicity
MH  - Microvessels/cytology/*drug effects/metabolism
MH  - Oxidative Stress/drug effects/physiology
OTO - NOTNLM
OT  - Brain endothelial cells
OT  - Isoflurane
OT  - NF-kappaB
OT  - Neuroinflammation
OT  - Oxidative stress
OT  - Ramelteon
EDAT- 2020/11/20 06:00
MHDA- 2021/11/30 06:00
CRDT- 2020/11/19 12:16
PHST- 2020/09/21 00:00 [received]
PHST- 2020/11/01 00:00 [accepted]
PHST- 2020/10/29 00:00 [revised]
PHST- 2020/11/20 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2020/11/19 12:16 [entrez]
AID - 10.1007/s12640-020-00309-7 [pii]
AID - 10.1007/s12640-020-00309-7 [doi]
PST - ppublish
SO  - Neurotox Res. 2021 Jun;39(3):677-686. doi: 10.1007/s12640-020-00309-7. Epub 2020 
      Nov 19.