Joseph C. Wu

Publication Details

  • Pretreatment with angiotensin-converting enzyme inhibitor improves doxorubicin-induced cardiomyopathy via preservation of mitochondrial function JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Hiona, A., Lee, A. S., Nagendran, J., Xie, X., Connolly, A. J., Robbins, R. C., Wu, J. C. 2011; 142 (2): 396-U529

    Abstract:

    Doxorubicin is a widely used chemotherapy drug, but its application is associated with cardiotoxicity. Free radical generation and mitochondrial dysfunction are thought to contribute to doxorubicin-induced cardiac failure. Angiotensin-converting enzyme inhibitors are commonly used as cardioprotective agents and have recently been shown in clinical studies to be efficacious in the prevention of anthracycline-induced heart failure. This study evaluated a mechanism for these protective effects by testing the ability of the angiotensin-converting enzyme inhibitor enalapril to preserve mitochondrial function in a model of chronic doxorubicin treatment in rats.Sprague Dawley rats were divided into 3 groups and followed for a total of 10 weeks: (1) control-untreated, (2) doxorubicin treated, and (3) doxorubicin + enalapril treated. Doxorubicin was administered via intraperitoneal injection at weekly intervals from weeks 2 to 7. Enalapril was administered in the drinking water of the doxorubicin + enalapril group for the study duration.Doxorubicin treatment produced a significant loss in left ventricular contractility (P < .05), decrease in mitochondrial function via impairment of state-3 respiration, decrease in the cytosolic fraction of adenosine triphosphate, and up-regulation of free radical production. Enalapril significantly attenuated the decrease in percent fractional shortening (P < .05) and prevented the doxorubicin-associated reduction in respiratory efficiency and cytosolic adenosine triphosphate content (P < .05). Enalapril also abolished the robust doxorubicin-induced increase in free radical formation.Administration of enalapril attenuates doxorubicin-induced cardiac dysfunction via preservation of mitochondrial respiratory efficiency and reduction in doxorubicin-associated free radical generation.

    View details for DOI 10.1016/j.jtcvs.2010.07.097

    View details for Web of Science ID 000292775200035

    View details for PubMedID 21094500

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