Antiapototic Effect of Tauroursodeoxycholic Acid Protects against Acute Doxorubicin Induced Cardiomyopathy in Rats
Background and purpose: Cardiotoxic carrdiomyopathy mediated by inflammation, oxidative stress lead to apoptosis with subsequently cell damage and heart failure. Tauroursodeoxycholic acid (TUDCA) is a bile acid that have anti-inflammatory and anti-oxidant effect, the current study aimed to examine the effect of administration of TUDCA on doxorubicin induced acute cardiomyopathy and explore the possible mechanism/s. Methods: Cardiomyopathy was induced in rats by single intraperitoneal (ip) injection of doxorubicin (DOX) (15 mg/kg). Results: doxorubicin administration exerted elevated levels of cereatine kinase-MB (CK-MB) and Lactate Dehydrogenase (LDH) in serum, in addition to myocardial TNF-α content, MDA levels, caspase-3, caspase-9 and caspase-12. However decrease in cardiac SOD and catalase content. Histopathological examination of myoendocardial section showed marked degeneration of cardiac muscle, distention of sarcoplasmic reticulum with marked accumulation of collagen fibers. Decrease immunoreactivity to antitroponin antibody. Echocardiography showed reduced LV fractional shortening, ejection fraction, and cardiac output. Treatment with TUDCA (250 mg/kg, ip) for 10 days significantly ameliorated histological changes and decreased the myocardium peroxidative damage in addition to decrease the cardiac markers for apoptosis. Conclusion: TUDCA can protect the heart from cardiotoxic effect of doxurubicin, The protective effects obtained by TUDCA is due to its inhibition of both endoplasmic stress and mitochondrial damage associated with chemotherapy treatment, with antioxidant and antiinflamatory properties. These results confirm the possible use of TUDCA to protect the heart during chemotherapy regimen.