Cyclic arginine-glycine-aspartate attenuates acute lung injury in mice after intestinal ischemia/reperfusion

Matsuo, Shingo; Yang, Weng‐Lang; Aziz, Monowar; Jacob, Asha; Wang, Ping

doi:10.1186/cc12493

Cited by 28 publications

(30 citation statements)

References 38 publications

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“…During airway inflammation, neutrophils are the first cells to be recruited and are the predominant cause of tissue damage [20]. Activated neutrophils induce extensive lung inflammation and the destruction of basement membrane and increase the permeability of alveolar capillary membrane [21].…”

Section: Discussionmentioning

confidence: 99%

Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

Liu

et al. 2014

BioMed Research International

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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.

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Section: Discussionmentioning

confidence: 99%

Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

Liu

et al. 2014

BioMed Research International

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“…Intestinal I/R was performed as previously described (4). Briefly, animals were placed on a heating pad and anesthetized with 2.5% inhalational isoflurane.…”

Section: Methodsmentioning

confidence: 99%

“…Tissue injury was assessed in a blinded fashion using a semi-quantitative light microscopy evaluation. The severity of gut injury was scored by assessing villus-to-crypt ratio (normal ratio, 5:1), lymphocytic infiltration, epithelial degeneration/necrosis, erosion, glandular dilatation, and transmural changes (4). Three separate cross-sections from the intestines of 3 mice in each treatment group were scored.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, intestinal I/R is characterized by a dramatic systemic inflammatory response and remote organ injury (3). Acute lung injury has been consistently associated with intestinal I/R injury (4, 5). The pathophysiology of lung injury is mediated by systemic inflammation secondary to the initial insult, which in turn causes recruitment of inflammatory cells, local endothelial cell injury, and smooth muscle dysfunction (6, 7).…”

Section: Introductionmentioning

confidence: 99%

“…To test this hypothesis, we used a well-established murine model of superior mesenteric artery occlusion (4). Animals were post-treated with SRT1720 at the time of reperfusion.…”

Section: Introductionmentioning

confidence: 99%

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Sirtuin 1 Activator Srt1720 Protects Against Organ Injury Induced by Intestinal Ischemia-Reperfusion

Hansen

Khader

Yang

et al. 2016

Shock

Self Cite

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Intestinal ischemia-reperfusion (I/R) occurs in various clinical situations and causes local and remote organ injury, especially in the lungs, leading to significant morbidity and mortality. Maintenance of mitochondrial biogenesis is essential for cell survival, and is regulated in part by sirtuin 1, an energy-sensing enzyme. We hypothesized that sirtuin 1 activation with SRT1720 would reduce local and remote organ injury after intestinal I/R. Intestinal I/R was induced by occlusion of the superior mesenteric artery of adult male C57BL/6 mice for 45 min, followed by reperfusion for 4 h. SRT1720 or vehicle was injected intravenously at the time of reperfusion. Blood, small intestine, and lung tissues were collected for analysis. SRT1720 treatment of I/R mice resulted in a 57% increase in protein levels of succinate dehydrogenase (SDH), an index of mitochondrial mass, and a 120% increase in mRNA levels of mitochondrial transcription factor A (TFAM), a marker for mitochondrial biogenesis. The microscopic architecture and apoptosis of the gut tissue was improved in the SRT1720-treated I/R mice. SRT1720 decreased intestinal mRNA levels of TNF-α by 60% and inducible nitric oxide synthase (iNOS) to baseline after I/R. Systemic inflammation, as determined by serum IL-6, was reduced in treated mice. Lung injury, as measured by histologic architecture and myeloperoxidase activity, and lung apoptosis were also improved after SRT1720 treatment. SRT1720 preserved mitochondrial biogenesis and mass, leading to inhibition of inflammation and oxidative stress, thereby protecting against intestinal I/R-induced injury. Thus, the sirtuin 1-mediated pathway is a promising target for treatment of intestinal I/R injury.

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Blockade of PKCβ protects against remote organ injury induced by intestinal ischemia and reperfusion via a p66shc-mediated mitochondrial apoptotic pathway

et al. 2014

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Intestinal ischemia-reperfusion (I/R) is a serious clinical dilemma with high morbidity and mortality. Remote organ damage, especially acute lung injury and liver injury are common complications that contribute to the high mortality rate. We previously demonstrated that activation of PKCβII is specifically involved in the primary injury of intestinal I/R. Considering the tissue-specific features of PKC activation, we hypothesized that some kind of PKC isoform may play important roles in the progression of secondary injury in the remote organ. Mice were studied in in vivo model of intestinal I/R. The activation of PKC isoforms were screened in the lung and liver. Interestingly, we found that PKCβII was also activated exclusively in the lung and liver after intestinal I/R. PKCβII suppression by a specific inhibitor, LY333531, significantly attenuated I/R-induced histologic damage, inflammatory cell infiltration, oxidative stress, and apoptosis in these organs, and also alleviated systemic inflammation. In addition, LY333531 markedly restrained p66shc activation, mitochondrial translocation, and binding to cytochrome-c. These resulted in the decrease of cytochrome-c release and caspase-3 cleavage, and an increase in glutathione and glutathione peroxidase. These data indicated that activated PKC isoform in the remote organ, specifically PKCβII, is the same as that in the intestine after intestinal I/R. PKCβII suppression protects against remote organ injury, which may be partially attributed to the p66shc-cytochrome-c axis. Combined with our previous study, the development of a specific inhibitor for prophylaxis against intestinal I/R is promising, to prevent multiple organ injury.

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Cyclic arginine-glycine-aspartate attenuates acute lung injury in mice after intestinal ischemia/reperfusion

Cited by 28 publications

References 38 publications

Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

Sirtuin 1 Activator Srt1720 Protects Against Organ Injury Induced by Intestinal Ischemia-Reperfusion

Blockade of PKCβ protects against remote organ injury induced by intestinal ischemia and reperfusion via a p66shc-mediated mitochondrial apoptotic pathway

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