Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNKp38 MAPK Signal Pathways
Joint Authors
Zhao, Min
Hu, Xiao
Shen, Haitao
Wang, Yu
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-04-05
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Paraquat (PQ) is a widely used herbicide with extremely high poisoning mortality mostly from acute lung injury (ALI) or progressive pulmonary fibrosis.
Toxicity mechanisms remain unclear, but a redox cycling process that generates reactive oxygen species (ROS) is involved, as are inflammation and cell apoptosis.
We established an ALI mouse model by intraperitoneal injection of PQ (28 mg/kg) and then investigated the effects of a potent liver X receptor (LXR) agonist, TO901317 (5 or 20 mg/kg), injected intraperitoneally 30 min after PQ administration.
Poisoned mice exhibited severe lung tissue lesions and edema, significant neutrophilic (PMNs) infiltration, and release of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).
PQ administration also decreased activity of antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferases (GSTs), and increased lipid peroxidation as evaluated by malondialdehyde (MDA) levels.
PQ exposure induced upregulation of the proapoptotic gene Bax and downregulation of the antiapoptotic gene Bcl-2, leading to marked cell apoptosis in the lung tissues.
TO901317 treatment reversed all these effects through inhibition of PQ-induced nuclear factor kappa B (NF-κB) and JNK/p38 mitogen-activated protein kinase (MAPK) activation.
The LXR agonist TO901317 had potent antioxidant, anti-inflammatory, and antiapoptotic effects against PQ-induced ALI.
American Psychological Association (APA)
Hu, Xiao& Shen, Haitao& Wang, Yu& Zhao, Min. 2017. Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNKp38 MAPK Signal Pathways. BioMed Research International،Vol. 2017, no. 2017, pp.1-13.
https://search.emarefa.net/detail/BIM-1137260
Modern Language Association (MLA)
Hu, Xiao…[et al.]. Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNKp38 MAPK Signal Pathways. BioMed Research International No. 2017 (2017), pp.1-13.
https://search.emarefa.net/detail/BIM-1137260
American Medical Association (AMA)
Hu, Xiao& Shen, Haitao& Wang, Yu& Zhao, Min. Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNKp38 MAPK Signal Pathways. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-13.
https://search.emarefa.net/detail/BIM-1137260
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1137260