Doksorubisinle indüklenen kardiyotoksisitede pimobendanın sitokin düzeylerine etkisi

Amaç: Doksorubisin (DOX) çeşitli insan kanserlerini tedavi etmede kullanılır, ancak kardiyotoksisitesi ve kalp yetmezliği etkileri nedeniyle kullanımı sınırlıdır. Pimobendan (PIMO) kalp yetmezliğini tedavi etmek için kullanılır. PIMO'nun proinflamatuar sitokinleri baskıladığı bildirilmesine rağmen, PIMO'nun kardiyotoksisitede antiinflamatuar sitokinler üzerindeki etkisi araştırılmadı. Bu çalışmanın amacı, PIMO'nun DOX ile indüklenen kardiyotoksisitede tümör nekrozis faktör-alfa (TNF-α), interlökin (IL)-6 ve IL-10 üzerindeki etkilerini belirlemektir. Gereç ve Yöntem: 54 adet erkek Swiss fare Kontrol (n:6), DOX (n:24) ve DOX+PIMO (n:24) olarak gruplandırıldı. Kontrol grubuna intraperitoneal (İP) ve gavaj yöntemiyle fizyolojik tuzlu su verildi. DOX grubuna IP olarak tek doz 18 mg / kg DOX ve DOX+PIMO grubuna IP olarak tek doz 18 mg / kg DOX ve gavaj yoluyla 5 gün boyunca 1 mg / kg PIMO uygulandı. DOX uygulamasından 2, 24, 72 ve 120 saat sonra genel anestezi altında kalpten kan örnekleri alındı. Sitokin seviyeleri ELISA yöntemiyle ölçüldü. Bulgular: Bu çalışma, DOX ile ilişkili kardiyotoksisiteye bağlı olarak proinflamatuar sitokinlerde artma ve antiinflamatuvar sitokinlerde azalma olduğunu gösterdi. PIMO uygulaması, TNF-α ve IL-6 artışını veya IL-10'un azalmasını engellemedi. Daha önce yapılan çalışmalar, kardiyotoksisitede PIMO'nun proinflamatuar sitokinler üzerindeki etkisine odaklanmıştır, ancak hiçbir çalışma PIMO'nun IL-10 düzeyindeki etkisini değerlendirmemiştir. İlginç bir şekilde, bu çalışmada, PIMO IL-10 seviyelerini arttırmadı. Öneri: PIMO'nun DOX ile indüklenen kardiyotoksisiteye karşı koruyucu bir etkisi olmadığı ifade edilebilir.

Effect of pimobendan on cytokine levels in doxorubicin-induced cardiotoxicity

Aim: Doxorubicin (DOX) is used to treat various human cancers, butits use is limited due to its cardiotoxicity and heart failure effects. Pimobendan(PIMO) is used to treat heart failure. Although PIMO hasbeen reported to suppress proinflammatory cytokines no studies haveinvestigated the effect of PIMO on antiinflammatory cytokines in cardiotoxicity.The purpose of this study was to determine the effects ofPIMO on tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 andIL-10 in the DOX-induced cardiotoxicity.Materials and Methods: The 54 male Swiss mice were categorized asControl (n:6), DOX (n:24), and DOX+PIMO (n:24). The Control groupreceived physiological saline solution intraperitoneally (IP) and gavage.DOX group received a single IP injection of 18 mg/kg DOX, andDOX+PIMO group received a single IP injection of 18 mg/kg DOX + 1mg/kg PIMO SID for 5 days by gavage. Blood samples were collectedfrom the heart by cardiac puncture under general anesthesia at 2, 24,72 and 120 h following DOX administration. Cytokines levels were measuredusing ELISA.Results: This study showed an increase in proinflammatory cytokinesand a decrease in antiinflammatory cytokines, dependent on DOXinducedcardiotoxicity. PIMO administration did not prevent TNF-αand IL-6 increase or IL-10 decrease. Previous studies have focused onthe effect of PIMO on proinflammatory cytokines in cardiotoxicity, butno study has evaluated the effect of PIMO on IL-10 level. Interestingly,in the present study, PIMO did not increase IL-10 levels.Conclusion: It may be stated that PIMO has no protective affect againstDOX-induced cardiotoxicity.

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