PMID- 34608599
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220502
IS  - 1559-0755 (Electronic)
IS  - 0257-277X (Linking)
VI  - 70
IP  - 1
DP  - 2022 Feb
TI  - Azilsartan attenuates lipopolysaccharide-induced acute lung injury via the 
      Nrf2/HO-1 signaling pathway.
PG  - 97-105
LID - 10.1007/s12026-021-09240-1 [doi]
AB  - Acute lung injury (ALI) is a severe complication of sepsis and hemorrhagic shock 
      with high morbidity. In the present study, the protective effect of Azilsartan on 
      lipopolysaccharide (LPS)-induced ALI in mice was investigated to explore the 
      potential therapeutic property of Azilsartan for the treatment of ALI. LPS was 
      used to induce an ALI model in mice. Hematoxylin-eosin (HE) staining sections 
      were then evaluated for the pathological state of lung tissues. Bronchoalveolar 
      lavage fluid (BALF) protein concentration, wet/dry weight ratios of lung tissues, 
      and pulmonary myeloperoxidase (MPO) activity were detected to determine the 
      degree of pulmonary injury. The number of total cells, macrophages, and 
      neutrophils in BALF were counted using a hemocytometer to illustrate the 
      inflammatory cell infiltration. The lung function was monitored using a 
      spirometer. The concentrations of interleukin-1beta (IL-1beta), monocyte 
      chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were determined using 
      enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated by the 
      superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) 
      concentrations in the lung tissue. The expressions of nuclear erythroid 2-related 
      factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined using Western blot 
      analysis. Azilsartan therapy alleviated LPS-induced lung tissue damage, increased 
      BALF protein concentration, lung wet to dry weight ratio, MPO activity, and 
      macrophage and neutrophils infiltration. Also, Azilsartan ameliorated the 
      production of inflammatory factors (IL-1beta, MCP-1, and IL-8). Azilsartan 
      ameliorated LPS-impaired lung SOD activity, the GSH concentration, and the MDA 
      concentration. Mechanistically, Azilsartan activated the LPS-impaired Nrf2/HO-1 
      signaling pathway. Azilsartan therapy attenuates LPS-induced ALI via the 
      Nrf2/HO-1 signaling pathway.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Zhang, Chengshi
AU  - Zhang C
AD  - Department of Respiratory, Punan Hospital, Pudong New Area, Shanghai, 200125, 
      China.
FAU - Zhao, Yunfeng
AU  - Zhao Y
AD  - Department of Respiratory, Punan Hospital, Pudong New Area, Shanghai, 200125, 
      China.
FAU - Yang, Xiaorong
AU  - Yang X
AUID- ORCID: 0000-0002-6263-9104
AD  - Department of Endocrinology, Punan Hospital, No.279, Linyi Road, Pudong New Area, 
      Shanghai, 200125, China. yangxiaorong556@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211004
PL  - United States
TA  - Immunol Res
JT  - Immunologic research
JID - 8611087
RN  - 0 (Benzimidazoles)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Oxadiazoles)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - F9NUX55P23 (azilsartan)
SB  - IM
MH  - *Acute Lung Injury/chemically induced/drug therapy
MH  - Animals
MH  - Benzimidazoles
MH  - Heme Oxygenase-1/metabolism/pharmacology/therapeutic use
MH  - Interleukin-8/metabolism
MH  - *Lipopolysaccharides/metabolism
MH  - Lung/pathology
MH  - Mice
MH  - NF-E2-Related Factor 2/metabolism/pharmacology/therapeutic use
MH  - Oxadiazoles
MH  - Signal Transduction
MH  - Superoxide Dismutase/metabolism/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Acute lung injury
OT  - Azilsartan
OT  - Inflammation
OT  - LPS
OT  - Nrf2
OT  - Oxidative stress
EDAT- 2021/10/06 06:00
MHDA- 2022/05/03 06:00
CRDT- 2021/10/05 06:45
PHST- 2021/07/12 00:00 [received]
PHST- 2021/09/25 00:00 [accepted]
PHST- 2021/10/06 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2021/10/05 06:45 [entrez]
AID - 10.1007/s12026-021-09240-1 [pii]
AID - 10.1007/s12026-021-09240-1 [doi]
PST - ppublish
SO  - Immunol Res. 2022 Feb;70(1):97-105. doi: 10.1007/s12026-021-09240-1. Epub 2021 
      Oct 4.