title: Protective effects of erythropoietin on endotoxin-related organ injury in rats.
abstract: The protective effect of erythropoietin (EPO) on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing endotoxin-induced organ damage. Rat model of multiple organ failure (MOF) was established by tail vein injection of 10 mg/kg lipopolysaccharide (LPS). Recombinant human EPO treatment (5000 U/kg) was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN) and creatinine (Cr), were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α) were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ultrastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein expression levels were detected by using Western blotting. EPO treatment showed a modest effect in preventing LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-α levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase (AKT) and increased nuclear factor-κB (NF-κB) activation in the lung, liver, and kidney (P<0.05 vs. control). However, EPO treatment significantly decreased the LPS-induced pAKT up-regulation in these tissues (P<0.05 vs. LPS treatment alone). The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways.
authors.affiliation: Intensive Care Unit, Tumor Hospital of Jilin Province, Changchun, 130012, China. dyjlxr@126.com.
authors.forename: Xiu-Jiang
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Intensive Care Unit, Tumor Hospital of Jilin Province, Changchun, 130012, China.
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Intensive Care Unit, Tumor Hospital of Jilin Province, Changchun, 130012, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Sun
authors.affiliation: Intensive Care Unit, Tumor Hospital of Jilin Province, Changchun, 130012, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Nephrology, First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Yang
authors.affiliation: Department of Nephrology, First Hospital of Jilin University, Changchun, 130021, China. kjkduyujun@126.com.
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Du
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D004731:Endotoxins; D004921:Erythropoietin / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D009102:Multiple Organ Failure / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt