Levosimendan prevents doxorubicin-induced cardiotoxicity in time- and dose-dependent manner: implications for inotropy.
MixedChemical/toxinWistar rats; C57BL/6 and 129 strain mice including phospholamban knockout miceFemale breast cancer-bearing mice; sex of rats not stated24 micrograms/kg cumulative or 24 micrograms/kg single bolusAdministered alongside doxorubicin over the 14-day sub-chronic protocol and the…
Model: Doxorubicin-induced sub-chronic and chronic cardiotoxicity (cumulative doxorubicin 18 mg/kg)
A single bolus of levosimendan abrogated doxorubicin cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/phospholamban signalling, with no protection in phospholamban knockout mice; cardioprotection persisted in the breast cancer-bearing model and was abolished by PKA inhibition in vitro.
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