Effect of pimobendan on cytokine levels in doxorubicin-induced cardiotoxicity

Abstract

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.