AYŞE ER, Burak DIK, Gül ÇETİN, FERAY ALTAN, KAMİL ÜNEY, MUAMMER ELMAS, Enver YAZAR

Etanersept - endotoksemi tedavisinde kullanılabilir mi?

Araştırmanın amacı endotoksemide etanersept uygulamasının kan sitokinler, fibrinojen, antitrombin, 13,14-dihidro-15-keto prostaglandin F2α ve biyokimyasal parametrelere etkisini araştırmaktır. Erişkin 126 adet Sprague Dawley ırkı erkek rat 3 gruba ayrılarak; 1. Gruba lipopolisakkarit (4 mg, IP), 2. Gruba etanersept (8 mg/kg, IP) ve 3. Gruba lipopolisakkarit + etanersept uygulamaları yapıldı. Uygulamalardan sonra 0., 1., 2., 4., 8., 12. ve 24. saatlerde kan örnekleri alındı. Serum tümör nekrozis faktör-α, interlöykin-1β, interlöykin-10 ve plazma 13,14-dihidro-15-keto-prostaglandin F2α düzeyleri ELISA okuyucusunda; sitratlı plazma antitrombin ve fibrinojen düzeyleri koagulometrede; serum biyokimyasal parametreleri otoanalizörde belirlendi. Etanerseptin fibrinojen düzeyinde düzensiz değişimlere ve 13,14-dihidro-15-keto-prostaglandin F2α, alkalen fosfataz ile alanin aminotransferaz düzeyinde yükselmelere neden olduğu belirlendi. Lipopolisakkarit uygulaması sitokinler, 13,14-dihidro-15-keto-prostaglandin F2α, fibrinojen, organ hasar belirteçleri ve trigliserit düzeylerinde yükselmelere neden olurken, antitrombin seviyesinde düzensiz değişimlere neden oldu. Lipopolisakkarit + etanersept uygulanan grupta sitokinler, 13,14-dihidro-15-keto-prostaglandin F2α ve fibrinojen düzeyinde yükselmeler, antirombin düzeyinde düzensiz değişimler gözlendi. Lipopolisakkarit uygulaması ile yükselen kreatin kinaz-MB düzeyinin etanersept tarafından tamamen, tümör nekrozis faktör-α yükselmesinin kısmen engellendiği ancak kanda kalış süresini uzattığı ve interlöykin-10 düzeyini daha fazla yükselttiği belirlendi. Sonuç olarak endotoksemide etanerseptin kalp üzerindeki koruyucu etkisi ve interlöykin-10 düzeyini yükseltmesi nedeni ile tek doz uygulamasının veteriner sahada faydalı olabileceği belirlendi.

Anahtar Kelimeler:

tümör nekroz faktör, alanin aminotransferaz, alkalin fosfotaz, bakteriyel toksinler, sitokin, endotoksemia, endotoksinler, enzim aktivitesi, enzimler, fibrinojen, interleukin 1, interleukin 10, lipopolisakkarit, farmakodinamik, farmakokinetik, farmakoloji, sıçan

Etanercept - can it be used in the treatment of endotoxemia?

Aim of this study was to investigate that effect of etanercept administration on the concentrations of cytokines, fibrinogen, antithrombin, 13,14-dihydro-15-keto-prostaglandin F2α and biochemical values in the endotoxemia. A totally male 126 Sprague Dawley rats were divided 3 equal groups; lipopolysaccharide (4 mg, IP), etanercept (8 mg/kg, IP) and lipopolysaccharide + etanercept were administered to Group 1, 2, and 3, respectively. Blood samples were collected at 0, 1, 2, 4, 8, 12 and 24th hours after treatments. Serum tumor necrosis factor-α, interleukin-1β, interleukin-10 and plasma 13,14-dihydro-15-keto-prostaglandin F2α levels were measured with ELISA reader, while antithrombin and fibrinogen levels were measured with coagulometer. Serum biochemical parameters were determined with auto-analyzer. Etanercept had irregular effect on the fibrinogen levels and it increased PGM, alkaline phosphatase and alanine aminotransferase activities. Lipopolysaccharide increased cytokines, PGM, fibrinogen, organ damage markers and triglyceride levels, and it had irregular effect on the antithrombin levels. Increased cytokines, PGM and fibrinogen levels were determined in lipopolysaccharide + etanercept group, but irregular changes were observed in antithrombin levels. Etanercept exactly depressed the increased creatine kinase-MB level and relatively depressed the increased tumor necrosis factor-α while it extended the presence of tumor necrosis factor-α, and it increased the elevated interleukin-10 levels by lipopolysaccharide. In conclusion, when protective effect of etanercept on the heart and increasing effect on the interleukin-10 levels in the endotoxemia is considered, single dose etanercept may be beneficial in the veterinary medicine.

Keywords:

tumour necrosis factor, alanine aminotransferase, alkaline phosphatase, bacterial toxins, cytokines, endotoxaemia, endotoxins, enzyme activity, enzymes, fibrinogen, interleukin 1, interleukin 10, lipopolysaccharides, pharmacodynamics, pharmacokinetics, pharmacology, rats,

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