Agmatine protects against zymosan-induced acute lung injury in mice by inhibiting NF-κB-mediated inflammatory response.

Abstract

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson's disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM) challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF)-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

• Authors: Xuanfei Li, Zheng Liu, He Jin, Xia Fan, Xue Yang, Wanqi Tang, Jun Yan, Huaping Liang
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 583736 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 25243152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• NF-kappa B
• Agmatine
• Zymosan
• Peroxidase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Acute Lung Injury (chemically induced, metabolism)
• Agmatine (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bronchoalveolar Lavage Fluid (chemistry)
• Cytokines (analysis)
• Lung (chemistry, drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (analysis, metabolism)
• Peroxidase (metabolism)
• Pneumonia
• Zymosan (toxicity)