Protective effect of CDP-choline on hypotension and tissue injury in septic shock model

Abstract

CDP-choline is an endogen molecule and also a drug that is used in several trauma and ischemic conditions. It has been demonstrated that it improves the hemodynamic parameters in different shock models and prevents tissue damage in rats. The current study tested the effect of CDP-choline on hypotension, inflammation and tissue injury induced by septic shock model in rats. Twenty-four adult, male Spraque-Dawley rats, weighing 250-300 g were used. Septic shock was induced by cecal ligation-incision (CLI). CDP-choline (100 mg/kg) injected intravenously (i.v.) at the 180th minute of the experiment. The animals were observed for 180 minutes after the injection, then blood and tissue samples were obtained for cytokine measurements and histological examinations, respectively. The cecal ligation-incision decreased arterial pressure and increased heart rate. Intravenous injection of CDP-choline reversed hypotension and increased arterial pressure up to control levels within the first 60 minutes without changing the increase in heart rate. The effect lasted for 3 hours. CDP-choline attenuated the increases in TNF-α, IL-1β and IL-6 levels in septic shock. Moreover, the drug exerted protective effects for the injury induced by septic shock in lungs, liver and kidney tissues; whereas this effect was not present on spleen. In conclusion, the present data suggested that intravenous CDP-choline administration can improve the deteriorations in hemodynamic and inflammatory parameters and can prevent the tissue injury in septic shock-induced by CLI in rats

Keywords

• CDP-choline
• cytokine
• multiple organ failure
• septic shock

CDP-kolin’in septik şok modelinde hipotansiyon ve doku hasarı üzerine koruyucu etkileri

Abstract

CDP-kolin, endojen bir molekül olmasının yanısıra travma ve iskemik koşullarda da kullanılan bir ilaçtır. Değişik şok modellerinde, sıçanlarda hemodinamik parametreleri iyileştirdiği ve doku hasarına karşı koruyucu etki gösterdiği ortaya konmuştur. Bu çalışmada, CDP-kolin’in sıçanlarda septik şokun neden olduğu hipotansiyon, inflamasyon ve doku hasarı üzerine olan etkileri incelendi. Deneylerde, ağırlıkları 250-300 g arasında değiş en 24 adet Spraque-Dawley ırkı erkek sıçan kullanıldı. Septik şok modeli oluşturmak için çekal bağlama-kesme yöntemi uygulandı. CDP-kolin (100 mg/kg), deneyin 180. dakikasında intravenöz (i.v.) olarak uygulandı. Hayvanlar enjeksiyon sonrası 180 dakika daha gözlendikten sonra sitokin ölçümleri ve histolojik incelemeler için sırasıyla kan ve doku örnekleri toplandı. Çekal bağlama-kesme kan basıncını azaltırken kalp atım sayısını artırdı. İntravenöz CDP-kolin uygulaması hipotansiyonu düzeltti ve arteryel basıncı ilk 60 dakika içerisinde, kalp hızındaki yüksekliği değiştirmeden, kontrol düzeylerine kadar artırdı. Etki 3 saat kadar sürdü. CDP-kolin, septik şoktaki TNF-α, IL-1β ve IL-6 düzeylerindeki yükselmeleri de azalttı. Bu etkilere ek olarak ilaç; akciğer, karaciğer ve böbreklerde (ancak dalakta değil) septik şokun sebep olduğu hasara karşı koruyucu etki gösterdi. Sonuç olarak mevcut veriler intravenöz CDP-kolin uygulamasının; çekal bağlama-kesme ile oluşturulan septik şokun neden olduğu hemodinamik ve inflamatuar parametrelerdeki bozukluklarda iyileşmeye ve meydana gelen doku hasarına karşı koruyucu olduğunu ortaya koymaktadır

Keywords

• CDP-kolin
• çoklu organ yetmezliği
• septik şok
• sitokin

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