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.

Agmatine Ameliorates Nicotine Induced Lung Injury in Rats through Decrease TGF-ß1 and Bax Immunoexpression and by Anti-oxidative Sress Pathway: Histological, Immunohistochemical and Biochemical Study

“…This improvement was obvious statistically by the significant increase in MLI and decrease in the mean alveolar thickness. These results were in conformity with Li et al [57] who found that AG treatment reduced myeloperoxidase activity in the lung tissue and the levels of TNF-, IL-1 , and also reduce IL-6 in lung and bronchoalveolar lavage fluid which in turn result in improvement of histological pictures of lung tissue. Furthermore, AG blocked the activation of nuclear factor (NF) -B indicating its anti-inflammatory effects.…”

“…Although, previous studies reported protective effect of AG on lung tissues [20], yet reports concerning the protecting effects of AG against NIC-induced lung injury needs more investigation. Therefore, the current study was designed to evaluate the influence of using AG on NIC-induced lung injury on the histological, immunohistochemical And Biochemical levels in rats aiming to explain its possible mechanisms.…”

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

“…In another study, agmatine was shown to attenuate LPS‐induced anorexia, sickness behaviour and IL‐6 and TNF‐α serum levels in rats . In an acute lung injury model, agmatine treatment reduced inflammation by inhibiting NF‐κB, and certain pro‐inflammatory cytokines such as TNF‐α, IL‐1β, IL‐6 . Restraint stress‐induced depressive‐like behaviour and hippocampal pro‐/anti‐oxidative homeostasis imbalance in mice were shown to be inhibited by agmatine treatment .…”

Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development

“…In addition, the delivery of zymosan into the airways is known to induce acute lung injury. 43 Recent studies report that CD8 + Trm in the lung develop within specific niches associated with tissue repair and remodelling, which occurs following infection. 21 The damage induced by this adjuvant and the corresponding "regeneration profile" associated with tissue injury repair is likely to further support lung Trm development.…”