Doxorubicin (DOX) demonstrated higher levels in heart tissue and greater intracellular accumulation in H9C2 cells compared to its metabolite DOXol, identifying DOX as the primary cytotoxic agent.
Doxorubicin is the primary cytotoxic agent in heart tissue compared to its metabolite doxorubicinol, likely due to its higher intracellular accumulation.
AIM: Doxorubicin (DOX) is an effective chemotherapeutic drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. Alcohol metabolite and doxorubicinol (DOXol) were the most prominent components in DOX-induced cardiotoxicity. It is necessary to elucidate the level of DOXol in heart in vivo and whether DOXol could cause toxicity at such a concentration. METHODS: The pharmacokinetics and heart distribution of DOX and its second metabolite DOXol were determined in rats. Based on this concentration level in vivo, H9C2 cell was used to examine the cardiotoxicity of DOX and DOXol. Real-time cell viability was determined using the xCelligence system and the membrane-permeable of DOX, and DOXol was also assessed by determining the intracellular and extracellular concentrations. RESULTS: Our data showed that DOX level was higher than DOXol level in heart tissue. DOX had a high level in intracellular H9C2 cell and was the primary cytotoxic agent. DOXol had a significantly low level in heart tissue and less cytotoxicity than that of DOX in H9C2. DOXol in heart could not diffuse from plasma but only form in the heart. DOXol could not enter cell as easy as DOX. The less cardiotoxicity of DOXol might be caused by the less intracellular concentration.
Zeng et al. (Wed,) conducted a other in Doxorubicin-induced cardiotoxicity. Doxorubicin (DOX) and doxorubicinol (DOXol) was evaluated on Pharmacokinetics, heart distribution, and cell viability. Doxorubicin (DOX) demonstrated higher levels in heart tissue and greater intracellular accumulation in H9C2 cells compared to its metabolite DOXol, identifying DOX as the primary cytotoxic agent.