Naloxone Protects against Lipopolysaccharide-Induced Neuroinflammation and Microglial Activation via Inhibiting ATP-Sensitive Potassium Channel

Autor: Xue Xue, Chunyan Liu, Zhang Anyu, Binbin Yuan, Fei Xu, Xiaobao Shao, Yijun Li, Shiwei Li, Zhijia Tang, Jun Wu, He Ping, Hucheng Chen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Lipopolysaccharides
Article Subject
Lipopolysaccharide
ATP-sensitive potassium channel
Narcotic Antagonists
Computer applications to medicine. Medical informatics
R858-859.7
Inflammation
(+)-Naloxone
Pharmacology
General Biochemistry
Genetics and Molecular Biology
Proinflammatory cytokine
Cell Line
Glibenclamide
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
KATP Channels
medicine
Animals
Neuroinflammation
Cell Proliferation
Mice
Inbred BALB C
General Immunology and Microbiology
Microglia
Behavior
Animal
Chemistry
Naloxone
Applied Mathematics
Anti-Inflammatory Agents
Non-Steroidal
Computational Biology
Neurodegenerative Diseases
General Medicine
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Modeling and Simulation
medicine.symptom
030217 neurology & neurosurgery
medicine.drug
Research Article
Zdroj: Computational and Mathematical Methods in Medicine
Computational and Mathematical Methods in Medicine, Vol 2021 (2021)
ISSN: 1748-6718
1748-670X
Popis: Aim. The aim of this study was to evaluate the anti-inflammatory effects and underlying mechanism of naloxone on lipopolysaccharide- (LPS-) induced neuronal inflammation and microglial activation. Methods. LPS-treated microglial BV-2 cells and mice were used to investigate the anti-inflammatory effects of naloxone. Results. The results showed that naloxone dose-dependently promoted cell proliferation in LPS-induced BV-2 cells, downregulated the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and proinflammatory enzymes iNOS and COX-2 as well as the expression of free radical molecule NO, and reduced the expression of Iba-1-positive microglia in LPS-stimulated BV-2 cells and mouse brain. Moreover, naloxone improved LPS-induced behavior degeneration in mice. Mechanically, naloxone inhibited LPS-induced activation in the ATP-sensitive potassium (KATP) channel. However, the presence of glibenclamide (Glib), an antagonist of KATP channel, ameliorated the suppressive effects of naloxone on inflammation and microglial activation. Conclusion. Naloxone prevented LPS-induced neuroinflammation and microglial activation partially through the KATP channel. These findings might highlight the potential of naloxone in neuroinflammation therapy.
Databáze: OpenAIRE
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