The therapeutic effects of thalidomide and etanercept on septic rats exposed to lipopolysaccharide

BACKGROUND: The aim of this study was to evaluate the therapeutic effects of thalidomide and etanercept on lipopolysaccharide (LPS)-induced sepsis in a rat model.
METHODS: Thirty male Wistar Albino rats were divided into 5 groups: Control, LPS, LPS+Thalidomide, LPS+Etanercept, and LPS+Thalidomide+Etanercept. The control group was given a 1 mL intraperitoneal (i.p.) injection of 0.9% saline solution. For endotoxic treatment, the rats were injected with a single i.p. dose of LPS (Escherichia coli 0111: B4 (5 mg/kg). Thalidomide (0.5 mg/kg) and etanercept (1 mg/kg) were administered i.p. to the therapeutic groups. Hepatic tissue tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and platelet-derived growth factor (PDGF) levels were determined by enzyme-linked immunosorbent assay and malondialdehyde (MDA) levels and total oxidant status (TOS) were measured using appropriate methods.
RESULTS: In vivo results exhibited elevated liver tissue TNF-α, IL-6, ICAM-1, PDGF, MDA, and TOS levels in the LPS-treated animals compared with the controls. The analysis of liver tissue supported the findings of biochemical alterations and indicated a therapeutic role for thalidomide and etanercept. Treatment of septic animals with these agents resulted in a remarkable decrease in the selected proinflammatory cytokines, angiogenic factors, and reactive oxygen parameters.
CONCLUSION: Restoration of cytokine balance and oxidant status to normal levels following treatment with selected therapeutic agents suggests that thalidomide and etanercept can help to avoid the potentially devastating effects of sepsis.

Talidomid ve etanersept’in lipopolisakkarite maruz býrakýlan septik sýçanlarda terapötik etkileri

AMAÇ: Bu çalýþmada lipopolisakkaritle (LPS) indüklenmiþ sýçan sepsis modelinde talidomid ve etanersept’in terapötik etkilerini deðerlendirmeyi amaçladýk.
GEREÇ VE YÖNTEM: Otuz adet erkek Wistar Albino sýçan; Kontrol, LPS, LPS+Talidomid, LPS+Etanersept ve LPS+Talidomid+Etanersept olmak üzere beþ gruba ayrýldý. Kontrol grubuna 1 mL %0.9’luk salin solüsyonu intraperitoneal (i.p.) olarak verildi. Endotoksik tedavi için sýçanlara LPS (Escherichia coli 0111: B4 (5 mg/kg), tek doz) i.p. olarak enjekte edildi. Terapötik gruplarý oluþturmak için talidomid (0.5 mg/kg) ve etanersept (1 mg/kg) i.p. olarak uygulandý. Hepatik doku tümör nekroz faktör-α (TNF-α), interlökin-6 (IL-6), hücreler arasý adezyon molekülü-1 (ICAM-1) ve platelet-türevli büyüme faktörü (PDGF) düzeyleri ELISA yöntemiyle, malondialdehid (MDA) düzeyi ile toplam oksidan kapasitesi (TOS) uygun yöntemler kullanýlarak ölçüldü.
BULGULAR: In vivo sonuçlar, kontrol ile karþýlaþtýrýldýðýnda LPS uygulanmýþ hayvanlarda karaciðer TNF-α, IL-6, ICAM-1, PDGF, MDA ve TOS düzeylerinin arttýðýný gösterdi. Karaciðer dokularýnýn analiziyle, biyokimyasal deðiþiklikler desteklendi ve talidomid ve etanersept’in terapötik rolünü kanýtladý. Septik hayvanlarýn bu tedavi ajanlarýyla tedavi edilmesiyle seçilen proenflamatuvar sitokinler, anjiyogenik faktörler ve reaktif oksijen parametrelerinde kayda deðer bir düþüþ gözlendi.
TARTIÞMA: Seçilen terapötik ajanlarýn tedavisini takiben sitokin dengesinin ve oksidan durumunun normale döndürülmesi, talidomid ve etanersept’in sepsisin yýkýcý etkilerinden kaçýnmaya yardýmcý olabileceðini düþündürmektedir.