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Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.

ABSTRACT: Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or supplemented with ethyl pyruvate. Resuscitation with ethyl pyruvate did not improve early hemodynamics but prevented hyperglycemia, the intrinsic coagulation pathway, serum aspartate aminotransferase, and myeloperoxidase in the major organs. Resuscitation with ethyl pyruvate provided an anti-inflammatory potential to restrain serum TNF and high-mobility group B protein 1 levels. Ethyl pyruvate inhibited nuclear factor [kappa]B in the spleen but not in the other major organs. In contrast, ethyl pyruvate inhibited NO in all the major organs, and it also inhibited TNF production in the major organs but in the lung and heart. The most significant effects were found in the terminal ileum where ethyl pyruvate inhibited cytokine production, restrained myeloperoxidase activity, preserved the intestinal epithelium, and prevented the systemic distribution of bacterial endotoxin. Ethyl pyruvate can provide therapeutic anti-inflammatory benefits to modulate splenic nuclear factor [kappa]B, restrain inflammatory responses, and prevent hyperglycemia, the intrinsic coagulation pathway, and organ injury in porcine hemorrhage without trauma.

SUBMITTER: Dong W

PROVIDER: S-EPMC2891599 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.

Dong WeiHong W Cai Bolin B Peña Geber G Pisarenko Vadim V Vida Gergely G Doucet Danielle D Lee Marlon M Sharpe Susan S Lu Qi Q Xu Da-Zhong DZ Ramos Laura L Deitch Edwin A EA Ulloa Luis L

Shock (Augusta, Ga.) 20100801 2

Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or ...[more]

PMID: 19953001

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Project description:BACKGROUND:Porcine cytomegalovirus (PCMV) is an immunosuppressive virus that mainly inhibits T-lymphocyte and macrophage immune functions; it has significantly damaged the farming industry. Although recent studies have shown that miRNAs play important roles in immune responses, the regulatory mechanisms of miRNAs during immunosuppressive virus infection remain unclear. METHODS:In this study, porcine small-RNA transcriptomes of PCMV-infected and uninfected vital organs were first characterised by high-throughput sequencing. miRDeep2 software was used to predict novel pig-encoded miRNAs. To verify the accuracy of the high-throughput sequencing results, stem-loop qRT-PCR was performed on 12 significantly DE miRNAs. The physical and functional interactions between the immune-related target genes of the DE miRNAs in PCMV-infected organs were analysed using the STRING database. RESULTS:In total, 306 annotated and 295 novel miRNAs were identified from PCMV-infected and uninfected porcine organs, respectively, through alignment with known Sus scrofa pre-miRNAs. Overall, 92, 107, 95, 77 and 111 miRNAs were significantly differentially expressed in lung, liver, spleen, kidney and thymus after PCMV infection, respectively. According to Gene Ontology enrichment analysis, target genes of the differentially expressed miRNAs associated with immune system processes, regulation of biological processes and metabolic processes were enriched in every sample. Integrated expression analysis of the differentially expressed miRNAs and their target mRNAs in PCMV-infected thymus showed that the significant differential expression of specific miRNAs under the pressure of PCMV infection in central immune organs interfered with the expression of genes involved in important immune-related signalling pathways, thus promoting the viral infection. CONCLUSIONS:This is the first comprehensive analysis of the responses of host small-RNA transcriptomes to PCMV infection in vital porcine organs. It provides new insights into the regulatory mechanisms of miRNAs during infection by immunosuppressive viruses.

Dataset Information

Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.

Publications

Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage.

Similar Datasets

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