Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Apocynin (Apo) suppresses the generation of reactive oxygen species that are implicated in lipopolysaccharide (LPS)-induced lung injury (LPSLI). We thus hypothesized that Apo may attenuate LPSLI. In addition, we explored the cellular and molecular mechanisms of Apo treatment in LPSLI. ⋯ In addition, Apo attenuated the increase in lung weight, bronchoalveolar lavage fluid albumin content, and the histopathologic lung injury score. In conclusion, LPSLI is associated with increased inflammatory responses, apoptosis, and coagulation. The administration of Apo attenuates LPSLI through downregulation of the inflammatory responses and apoptosis.
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Cardiovascular collapse is the major factor contributing to the mortality of trauma-hemorrhage (T-H) patients. Toll-like receptors (TLRs) play a critical role in T-H-induced cardiac dysfunction. This study evaluated the role of TLR9 agonist, CpG-oligodeoxynucleotide (ODN) 1826, in cardiac functional recovery after T-H. ⋯ Our data suggest that CpG-ODN significantly attenuates T-H-induced cardiac dysfunction. The mechanisms involve activation of both PI3K/Akt and ERK signaling pathways. The TLR9 agonist, CpG-ODN 1826, may provide a novel treatment strategy for preventing or managing cardiac dysfunction and enhancing recovery in T-H patients.
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Large surface area burn injuries lead to activation of the innate immune system, which can be blocked by parasympathetic inputs mediated by the vagus nerve. We hypothesized that vagal nerve stimulation (VNS) would alter the inflammatory response of peritoneal macrophages after severe burn injury. Male BALB/c mice underwent right cervical VNS before 30% total body surface area steam burn and were compared with animals subjected to burn alone. ⋯ We identified a protective role for VNS in blocking peritoneal macrophage activation. Analysis of the phosphorylation state of nuclear factor κB pathway mediator, p65 Rel A, revealed a VNS-mediated reduction in p65 phosphorylation levels after exposure to LPS compared with burn alone. In combination, these studies suggest VNS mediates the inflammatory response in peritoneal macrophages by affecting the set point of LPS responsiveness.
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Previous studies have shown that PI3K/GSK-3β/β-catenin signaling pathway plays a vital role in ischemic preconditioning. The present study attempts to evaluate whether PI3K/GSK-3β/β-catenin signaling pathway might be responsible for the cardioprotection in ischemic postconditioning. Male Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. ⋯ It was found that Post and SB + I/R reduced infarct size (32.3% [SD, 2.8%], 32.7% [SD, 2.1%], vs. 53.4% [SD, 3.2%], respectively, P < 0.05) and apoptotic index of cardiomyocytes (23.2% [SD, 1.8%], 23.8% [SD, 1.8%], vs. 47.3% [SD, 5.8%], respectively, P < 0.05); compared with I/R, wortmannin abolished the cardioprotection of ischemic postconditioning. Post and SB + I/R increased phosphorylated Akt, phosphorylated GSK3β, β-catenin in cytosol and nucleus, and Bcl-2 expression versus I/R. These results indicate that ischemic postconditioning could induce myocardial protection via PI3K/GSK-3β/β-catenin signaling pathway, activation of which results in accumulation of β-catenin and upregulation of its target genes Bcl-2.
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Malic acid, in the form of its anion malate, is a key intermediate in the major biochemical energy-producing cycle known as the citric acid or Krebs cycle. In this study, the authors investigated the protective effect of a novel crystalloid solution of Ringer's malate following fluid resuscitation of hemorrhagic shock using a rat model. Under general anesthesia, Sprague-Dawley male rats were subjected to 60 min of hemorrhagic shock (40 mmHg for 60 min) followed by crystalloid resuscitation. ⋯ Histopathology indicated that Ringer's malate can protect against the multiple organ injury caused by hemorrhagic shock in rats. Ringer's malate prevented circulatory failure and alleviated multiple organ dysfunction syndrome in animals with hemorrhagic shock. The study suggests that Ringer's malate solution could be a potential novel therapeutic agent for fluid resuscitation.