PMID- 35598975
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20220804
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 45
IP  - 8
DP  - 2022 Aug 1
TI  - Selexipag Improves Lipopolysaccharide-Induced ARDS on C57BL/6 Mice by Modulating 
      the cAMP/PKA and cAMP/Epac1 Signaling Pathways.
PG  - 1043-1052
LID - 10.1248/bpb.b21-01057 [doi]
AB  - Selexipag, a long-acting and selective prostacyclin (PGI(2)) IP receptor agonist, 
      has in aged rats with stroke revealed effects of inhibiting inflammation, 
      ameliorating damage to the blood-brain barrier, and alleviating oxidative stress. 
      However, in the case of acute respiratory distress syndrome (ARDS) characterized 
      by diffuse alveolar damage and lung capillary endothelial injury, its effects yet 
      remain unknown. In this study, we investigated effects of the prophylaxis by 
      Selexipag on a mouse model of ARDS established by the lipopolysaccharide (LPS) 
      challenge and potential mechanism. Compared to the LPS-challenged mice, the 
      LPS-challenged mice with the prophylaxis by 0.5 or 1 mg/kg of Selexipag exhibited 
      significantly alleviated lung histological manifestations, reduced protein 
      leakage, decreased levels of interleukin (IL)-1beta, IL-6, and monocyte chemotactic 
      protein-1 (MCP-1), diminished expressions of E-selectin and vascular cell 
      adhesion molecule-1 (VCAM-1) mRNA, noticeably increased expressions of zonula 
      occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) protein, 
      escalated lung cAMP levels, and raised levels of lung relative 
      phosphorylated-protein kinase A catalytic subunit (p-PKA C) at Thr197 and 
      exchange protein activated by cAMP 1 (Epac1) protein. These results suggest that, 
      through suppressing inflammation and reducing vascular endothelial damage, 
      Selexipag can effectively ameliorate the LPS-induced ARDS on mice. The lung cAMP 
      and its downstream signaling modules, PKA and Epac1, possibly constitute the main 
      regulative molecular mechanism. Selexipag appears to hold promise to become a new 
      potential therapeutic option for ARDS.
FAU - Chen, Hongliu
AU  - Chen H
AD  - Department of Emergency, the First Affiliated Hospital of Guangxi Medical 
      University.
FAU - Shen, Ying
AU  - Shen Y
AD  - General Practice School, Guangxi Medical University.
FAU - Liang, Yi
AU  - Liang Y
AD  - Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi 
      Medical University.
FAU - Qiu, Ying
AU  - Qiu Y
AD  - Department of Emergency, the First Affiliated Hospital of Guangxi Medical 
      University.
FAU - Xu, Meili
AU  - Xu M
AD  - Department of Emergency, the First Affiliated Hospital of Guangxi Medical 
      University.
FAU - Li, Chaoqian
AU  - Li C
AD  - Department of Emergency, the First Affiliated Hospital of Guangxi Medical 
      University.
LA  - eng
PT  - Journal Article
DEP - 20220520
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Acetamides)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyrazines)
RN  - 5EXC0E384L (selexipag)
SB  - IM
MH  - *Acetamides/pharmacology
MH  - Animals
MH  - Inflammation/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Lung/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Pyrazines/pharmacology
MH  - *Respiratory Distress Syndrome/chemically induced/drug therapy
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Selexipag
OT  - acute respiratory distress syndrome
OT  - exchange protein activated by cAMP 1 (Epacl)
OT  - protein kinase A (PKA)
EDAT- 2022/05/23 06:00
MHDA- 2022/08/03 06:00
CRDT- 2022/05/22 21:23
PHST- 2022/05/23 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/05/22 21:23 [entrez]
AID - 10.1248/bpb.b21-01057 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2022 Aug 1;45(8):1043-1052. doi: 10.1248/bpb.b21-01057. Epub 
      2022 May 20.