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• W2024881956 abstract "Background Clinical use of doxorubicin is greatly limited by its severe cardiotoxic side effects. L-carnitine is a vitamin-like substance which has been successfully used in many cardiomyopathies, however, the intracellular mechanism(s) remain unclear. The objective of this study was set to evaluate the protective effect of L-carnitine on doxorubicin-induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s). Methods Primary cultured neonatal rat cardiomyocytes were treated with doxorubicin (1 µM) with or without pretreatment with L-carnitine (1–30 mM). Lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and flow cytometry measurement were used to assess cytotoxicity and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and chemiluminescence assay of superoxide production were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the quantity of cleaved caspase-3, cytosol cytochrome c, and Bcl-xL expression. Results L-carnitine inhibited doxorubicin-induced reactive oxygen species generation and NADPH oxidase activation, reduced the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased Bcl-xL expression, resulting in protecting cardiomyocytes from doxorubicin-induced apoptosis. In addition, L-carnitine was found to increase the prostacyclin (PGI2) generation in cardiomyocytes. The siRNA transfection for PGI2 synthase significantly reduced L-carnitine-induced PGI2 and L-carnitine's protective effect. Furthermore, blockade the potential PGI2 receptors, including PGI2 receptors (IP receptors), and peroxisome proliferator-activated receptors alpha and delta (PPARα and PPARδ), revealed that the siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of L-carnitine. Conclusions These findings suggest that L-carnitine protects cardiomyocytes from doxorubicin-induced apoptosis in part through PGI2 and PPARα-signaling pathways, which may potentially protect the heart from the severe toxicity of doxorubicin." @default.
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• W2024881956 date "2011-01-01" @default.
• W2024881956 modified "2023-10-10" @default.
• W2024881956 title "L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes" @default.
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• W2024881956 doi "https://doi.org/10.1016/j.ijcard.2009.06.010" @default.
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