α-Bisabolol: A Dietary Sesquiterpene that Attenuates Apoptotic and Nonapoptotic Cell Death Pathways by Regulating the...

Area of Science:

• Cardiology
• Pharmacology
• Toxicology

Background:

• Doxorubicin (DOX) chemotherapy can cause severe cardiotoxicity, limiting its use.
• Understanding the molecular mechanisms of DOX cardiotoxicity is crucial for developing protective strategies.

Purpose of the Study:

• To investigate the cardioprotective effects of α-bisabolol (BSB) against DOX-induced cardiotoxicity in a rat model.
• To elucidate the underlying pharmacological and molecular pathways involved in BSB's protective action.

Main Methods:

• Acute cardiotoxicity was induced in rats using a single intraperitoneal injection of DOX.
• Rats received oral administration of BSB twice daily for 5 days.
• Cardiac damage was assessed via cardiospecific markers, enzyme mapping, and molecular analyses of oxidative stress, mitochondrial function, ER stress, and apoptosis.

Main Results:

• DOX administration significantly damaged cardiac tissues, indicated by altered biomarkers and enzyme activity.
• DOX induced mitochondrial oxidative stress, DNA damage, impaired mitochondrial biogenesis and function, ER stress, Hippo signaling alterations, and various forms of cell death (apoptosis, necroptosis, ferroptosis).
• BSB treatment preserved myocardial integrity, reversing DOX-induced cellular, molecular, and structural damage.

Conclusions:

• α-bisabolol (BSB) demonstrates significant cardioprotective effects against doxorubicin (DOX)-induced cardiotoxicity in rats.
• BSB's protective mechanism involves potent antioxidant, anti-lipid peroxidative, and antiapoptotic activities.
• These effects are mediated through beneficial modulation of multiple signaling pathways, offering a promising therapeutic avenue.