Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal excretion of organic anions such as para-aminohippurate is reduced during severe sepsis and following ischemia/reperfusion injury. In order to better define the pathophysiology of sepsis-associated renal tubular dysfunction we measured the effect of lipopolysaccharide on renocortical organic anion transporter (OAT) expression in the rat. Prostaglandin E2 (PGE2) downregulates OATs in vitro, therefore, we also evaluated the effect of the cyclooxygenase (COX)-2 inhibitor parecoxib on this process. Endotoxemia caused a time- and dose-dependent decrease of OAT1 and OAT3 expression that paralleled increased renocortical COX-2 expression and PGE2 formation. Pretreatment with parecoxib decreased endotoxin-stimulated PGE(2) formation. Parecoxib attenuated OAT1 and OAT3 gene repression in the rat kidney following endotoxin treatment and during ischemia/reperfusion-induced acute renal injury. COX-2 inhibition improved the creatinine clearance in lipopolysaccharide-treated rats but not after ischemia/reperfusion-induced acute renal injury. The decreased clearance of para-aminohippurate in rats following endotoxin- or ischemia/reperfusion-induced renal injury was improved by parecoxib. Our findings show that COX-2 derived prostanoids downregulate OATs during lipopolysaccharide-induced acute renal injury.
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PMID:COX-2 inhibition attenuates endotoxin-induced downregulation of organic anion transporters in the rat renal cortex. 1894 99

Sepsis caused by uncontrolled systemic inflammation is one of the leading causes of death around the world. Parecoxib is a selective COX-2-specific inhibitor which has been demonstrated to possess anti-inflammatory and antiseptic functions in an animal sepsis model. The present study was performed to examine the therapeutic efficacy of parecoxib against inflammation in a mouse model of cecal ligation and puncture (CLP). Male mice were randomly divided into Sham, Model (Sepsis), Dexmedetomidine (Dex), and Parecoxib groups, with 12 mice in each group. After surgery, parecoxib (0.1, 1 and 10 mg/kg) was intraperitoneally injected and survival rates were then measured. The levels of immunoglobulin and inflammatory factors in sera and spleen were measured by enzyme-linked immunosorbent assay (ELISA), Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Subtypes of lymphocyte subsets were detected by flow cytometry. Hematoxylin-eosin staining was performed to examine spleen injury. We discovered that parecoxib treatment improved survival rates in mice with sepsis, with the effect increasing with concentration. Compared with the model group, the amount of immunoglobulin was increased, inflammatory factor production was inhibited, proportions of T helper and regulatory T cells were reduced, pathological damage in mice spleen was ameliorated, COX-2 expression was inhibited, and phosphorylated-p65 (p-p65) was deactivated in the spleen of the mice treated with Dexmedetomidine (DEX) and Parecoxib. Our data suggest that Parecoxib inhibits the inflammatory response and has protective effects against sepsis in mice, and may have potential as a novel therapeutic method for treating sepsis.
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PMID:Parecoxib inhibits inflammatory responses in a mouse model of sepsis. 3224 83