New Insights into Baricitinib's Immunomodulatory Role in Doxorubicin-induced Cardiomyopathy: JAK/STAT and TLR-4/NF-κB Pathways

Area of Science:

• Cardiology
• Immunology
• Pharmacology

Background:

• Doxorubicin-induced cardiomyopathy (DIC) is a significant clinical concern.
• Janus kinase (JAK) inhibitors, like baricitinib, modulate immune-inflammatory responses.
• Angiotensin receptor blockers (ARBs) are used in treating DIC.

Purpose of the Study:

• To investigate the cardioprotective potential of baricitinib in doxorubicin-induced cardiomyopathy (DIC).
• To elucidate baricitinib's immunomodulatory effects on JAK/STAT and TLR-4/NF-κB pathways in DIC.
• To compare baricitinib's efficacy with olmesartan, an ARB, in managing DIC.

Main Methods:

• Male albino rats were divided into five groups: control, doxorubicin, baricitinib, olmesartan, and combination treatment.
• Doxorubicin was administered to induce cardiomyopathy.
• Baricitinib and olmesartan were administered orally for 10 days.
• Histopathological, biochemical, and molecular analyses were performed to assess cardioprotection and pathway modulation.

Main Results:

• Baricitinib exhibited significant cardioprotective effects on histopathological and biochemical levels compared to the doxorubicin group.
• Baricitinib downregulated the JAK/STAT pathway by decreasing p-JAK2 and p-STAT1/3 levels.
• Baricitinib also downregulated the TLR-4/NF-κB pathway, reducing TLR-4 and NF-κB expression, and subsequently decreasing IL-6, TNF-α, VEGF-α, and NO levels.

Conclusions:

• Baricitinib demonstrates a novel cardioprotective role against doxorubicin-induced cardiomyopathy through modulation of JAK/STAT and TLR-4/NF-κB immune-inflammatory pathways.
• Baricitinib effectively reduces inflammation and angiogenesis markers associated with DIC.
• While olmesartan also provides cardioprotection, baricitinib shows superior anti-inflammatory effects, highlighting its therapeutic potential for DIC.