Ischemia reperfusion injury in the isolated hemoperfused bovine uterus--a model for the investigation of anti-inflammatory substances?
The inflammation model of the isolated hemoperfused bovine uterus was used to introduce a new in vitro model for the investigation of anti-inflammatory substances. As previous studies demonstrated both an increase in PGE2 synthesis and an up-regulation of COX-2 and iNOS mRNA by ischemia-reperfusion injury in the model (Braun and Kietzmann, 2004), inhibitory effects of the glucocorticoid dexamethasone, the NSAID flunixin and the selective COX-2 inhibitor DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)-phenyl-2-(5H)-furanone) were studied. All substances caused a significant decrease in tissue PGE2 production, while none induced down-regulation of COX-2 mRNA. A slight decrease in the mRNA level of iNOS was observed after 300 minutes of perfusion with dexamethasone-supplemented perfusion medium. In conclusion, the suitability of the isolated hemoperfused bovine uterus for the investigation of anti-inflammatory substances, especially regarding their COX-2 selectivity, was demonstrated. Use of the isolated hemoperfused bovine uterus in pharmacological research and drug screening may contribute to a reduction of animal testing.
Braun
Michael
M
Institut für Pharmacologie, Toxicologie und Pharmazie, Tierärztliche Hochschule, D-Hannover, Germany. Michael.Braun@tiho-hannover.de
Kietzmann
Manfred
M
D000826:Animal Testing Alternatives; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002417:Cattle; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014599:Uterus / Q000098:blood supply / Q000166:cytology* / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone