Hydropersulfides (RSSH) attenuate doxorubicin-induced cardiotoxicity while boosting its anticancer action

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Doxorubicin (DOX) chemotherapy frequently causes lethal cardiotoxicity.
• Reactive sulfur species (RSSH) are investigated for their potential protective roles.

Purpose of the Study:

• To determine if hydropersulfides (RSSH) can protect against doxorubicin-induced cardiotoxicity.
• To elucidate the protective mechanisms of RSSH in cardiac cells.
• To investigate the effect of RSSH on the anticancer efficacy of doxorubicin.

Main Methods:

• H9c2 cardiac cells were treated with doxorubicin (DOX) and hydropersulfides (RSSH).
• Reactive oxygen species (ROS) levels, Nrf2 and PGC-1α pathways, and caspase-3 activity were assessed.
• Anticancer effects were evaluated in three cancer cell lines with RSSH supplementation.

Main Results:

• RSSH supplementation significantly reduced DOX-induced cardiotoxicity in H9c2 cells.
• RSSH alleviated ROS surge, activated Nrf2-dependent antioxidant pathways, and PGC-1α.
• RSSH inhibited apoptosis by decreasing caspase-3 activity and potentiated DOX's anticancer effects.

Conclusions:

• Hydropersulfides (RSSH) are effective in mitigating doxorubicin-induced cardiotoxicity.
• RSSH exert protective effects by modulating oxidative stress, mitochondrial function, and apoptosis.
• RSSH may offer a dual benefit of reducing cardiotoxicity and enhancing chemotherapy efficacy.