PMC:4277126 / 47037-49944 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4277126","sourcedb":"PMC","sourceid":"4277126","source_url":"http://www.ncbi.nlm.nih.gov/pmc/4277126","text":"Doxorubicin-induced cardiotoxicity\nDoxorubicin (DOX) is a potent antitumor agent, but its dose-dependent cardiotoxicity limits its clinical use. DOX-induced cardiotoxicity involves the formation of free radicals and amplification of mitochondrial dysfunction. Due to relatively lower levels of CAT and the readily deactivated GPx in the cardiomyocytes, the heart is more susceptible to oxidative damage than other tissues. As an antioxidant, the cardioprotective effect of LBPs has been demonstrated in acute DOX-induced cardiotoxicity in rats66 and beagle dogs.65 Inhibition of oxidative stress is thought to be the main mechanism of the cardioprotective effects of LBPs. Xin et al66 suggested that LBPs might protect against DOX-induced cardiotoxicity through antioxidant-mediated mechanisms.\nXin et al65 conducted a mechanistic study in male Sprague–Dawley rats to explore the protective effect of LBPs on DOX-induced cardiotoxicity. Rats were administered orally with 200 mg/kg/day LBPs for 10 continuous days. About 10 mg/kg DOX was administered to rats via intravenous injection at day 7. At the end of the experiment, the rats were sacrificed with hearts promptly removed for biochemical and histological analysis. The results showed that pretreatment with 200 mg/kg LBPs for 10 days significantly reduced DOX-induced oxidative injury in cardiac tissue and significantly attenuated DOX-induced cardiac cytoplasmic vacuolization and myofibrillar disarrangement.65 LBP pretreatment decreased heart MDA level and increased heart SOD and GPx activities in DOX-treated rats. LBPs decreased the levels of serum CK and partially reversed DOX-induced bradycardia and prolonged QT interval as determined by electrocardiography.65 Furthermore, the cytotoxic study in vitro showed that 100 µg/mL LBPs protected against cytotoxicity of DOX in cardiac myoblasts H9c2. Incubation of human lung carcinoma A549 cells with 200 µg/mL LBPs did not alter the antiproliferative activity of DOX. These data indicated that LBPs elicit a potent protective effect on DOX-induced cardiomyocyte damages mainly via antioxidative and free radical-scavenging pathways.\nXin et al64 carried out a further study in beagle dogs to examine if LBPs alleviated DOX-induced cardiotoxicity. Intravenous administration of 15 mg/kg DOX significantly induced acute cardiotoxicity in beagle dogs characterized by conduction abnormalities including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia and increased serum CK and aspartate aminotransferase (AST).64 Oral pretreatment with 20 mg/kg body weight LBPs daily for 7 days effectively alleviated both DOX-induced conduction abnormalities and increased serum CK and AST.64 All these results confirm and extend previous observations in rats concerning the protective effect of LBPs against DOX-induced 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