Key result
Glutathione prevented doxorubicin-induced cardiotoxicity by reducing ROS generation and apoptosis, and restoring cell viability and function via the pERK signaling pathway.
Why the study?
Doxorubicin causes cardiotoxicity via cardiomyocyte death and dysfunction, motivating the investigation of antioxidant drugs such as glutathione to protect cardiac cells.
Does glutathione protect against doxorubicin-induced cardiotoxicity in human cardiac progenitor cells and a mouse model?
Does glutathione protect against doxorubicin-induced cardiotoxicity in human cardiac progenitor cells and a mouse model?
Glutathione protects against doxorubicin-induced cardiotoxicity in human cardiac progenitor cells and a mouse model by reducing reactive oxygen species and regulating pERK signaling.
Hypothesis-generating for glutathione in doxorubicin cardiotoxicity; leaves open clinical translation of pERK effects from animal data.
Cardiotoxicity caused by doxorubicin (DOX) is an important issue to consider for both patients and doctors who require DOX. DOX-induced cardiotoxicity is closely associated with cardiomyocyte death and dysfunction. To prevent DOX-induced cardiotoxicity, many studies have been conducted on new therapeutic strategies, including the discovery of novel functional modulators such as antioxidant drugs to restore the loss of function of transplanted or residual cardiac cells in the heart. We investigated whether glutathione (GSH), an antioxidant drug, has a protective effect against DOX-induced cardiotoxicity by decreasing ROS and unraveling the underlying molecular mechanisms. GSH clearly increased the viability of damaged human cardiac progenitor cells (hCPCs) treated with DOX. In addition, ROS generation and apoptosis induced by DOX treatment were significantly reduced. We also observed that GSH restored the capacity of hCPCs, as shown by the wound healing assay, transwell migration, and tube formation. We checked that GSH treatment restored the level of pERK, which increased in the DOX-treated group. The ERK inhibitor, U0126, increased the viability of damaged hCPCs. These data suggest that the restoration mechanism of GSH may be via the regulation of pERK signaling. We confirmed the effects of DOX and GSH using an in vivo model. As a result, GSH was confirmed to have a protective effect against DOX-induced cardiotoxicity through body weight, survival rate, histology, and mRNA level. Taken together, GSH prevents DOX-induced cardiotoxicity and regulates pERK signaling. GSH may be an effective therapeutic strategy for DOX-induced cardiotoxicity.
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Lee et al. (2023) studied Doxorubicin-induced cardiotoxicity. Glutathione vs. Doxorubicin alone was evaluated on Cell viability and ROS generation. Glutathione prevented doxorubicin-induced cardiotoxicity by reducing ROS generation and apoptosis, and restoring cell viability and function via the pERK signaling pathway.
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