Sotagliflozin ameliorates doxorubicin-induced cardiomyopathy by regulating inflammation and mitochondrial dysfunction...

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• Doxorubicin (DOX) is a chemotherapy agent that can induce experimental heart failure.
• Sotagliflozin (SOTA), a dual inhibitor of sodium-glucose co-transporters 1 and 2 (SGLT1/2), has shown cardiovascular benefits in diabetic patients.

Purpose of the Study:

• To investigate the cardioprotective mechanisms of Sotagliflozin (SOTA) against doxorubicin (DOX)-induced heart failure both in vitro and in vivo.

Main Methods:

• In vivo: C57BL/6 mice received multiple DOX doses; cardiac function and signaling were assessed with SOTA treatment.
• In vitro: H9C2 cells were treated with DOX and SOTA to evaluate cell viability, mitochondrial function, inflammation, oxidative stress, and cell death pathways.

Main Results:

• SOTA treatment in vivo improved cardiac function, reduced fibrosis, apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction.
• In vitro, SOTA enhanced H9C2 cell viability and mitigated DOX-induced apoptosis, inflammation, oxidative stress, and mitochondrial damage.
• SOTA reduced cleaved caspase-3, inflammatory cytokines (IL-6, IL-1β, TNF-α), reactive oxygen species, and mitochondrial Ca²⁺ loading, while improving mitochondrial function (JC-1, Bcl-2/Bax ratio).

Conclusions:

• Sotagliflozin (SOTA) exhibits significant cardioprotective effects against doxorubicin-induced cardiomyopathy.
• SOTA activates AMPK and inhibits mTOR signaling, contributing to its protective mechanisms against heart failure.
• SOTA represents a promising therapeutic agent for treating heart failure, particularly in the context of chemotherapy-induced cardiotoxicity.