Targeting PPARs Signaling Pathways in Cardiotoxicity by Natural Compounds

Area of Science:

• Cardiology
• Molecular Biology
• Pharmacology

Background:

• Cardiotoxicity, a significant complication of drugs and chemicals, impacts patient morbidity, quality of life, and mortality.
• Lipid accumulation and inflammation are key contributors to the development of cardiotoxicity.
• Peroxisome proliferator-activated receptors (PPARs) regulate cardiac genes involved in lipid/glucose metabolism and inflammation.

Purpose of the Study:

• To review the literature on naturally occurring chemicals (NCs) that protect against cardiotoxicity.
• To explore the mechanisms by which NCs modulate cardiotoxicity via PPARs.
• To examine the role of specific signaling pathways in NC-mediated cardioprotection.

Main Methods:

• Literature review of studies investigating NCs and cardiotoxicity.
• Analysis of research focusing on PPAR isoforms (PPARα, PPARγ, PPARβ/δ) in cardiac function.
• Examination of signaling pathways including AMPK/PGC-1α/PPARα, PPARα/NF-κB, and PPARγ/Nrf2/HO-1/NF-κB.

Main Results:

• Several NCs demonstrate protective effects against cardiotoxicity.
• Targeting PPARα and PPARγ by NCs is a key mechanism for cardioprotection.
• NCs modulate complex signaling cascades involving AMPK, PGC-1α, NF-κB, Nrf2, and HO-1.

Conclusions:

• Naturally occurring chemicals offer a promising therapeutic avenue for preventing or treating cardiotoxicity.
• Modulation of PPARs and associated signaling pathways is crucial for the cardioprotective effects of NCs.
• Further research into NCs can lead to novel strategies for managing drug-induced heart damage.