Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against...

Area of Science:

• Biochemistry
• Cardiology
• Toxicology

Background:

• Catecholamines can oxidize, forming reactive intermediates and reactive oxygen species (ROS), leading to oxidative stress and cell damage.
• Iron chelation shows promise for cardioprotection against catecholamine toxicity, but traditional chelators can disrupt iron homeostasis.
• Prochelators offer a safer alternative, activating only under conditions of oxidative stress.

Purpose of the Study:

• To evaluate the novel prochelator BHAPI and its active form HAPI for protecting cardiac cells from catecholamine-induced cardiotoxicity.
• To investigate the mechanism of BHAPI activation by ROS and its iron-chelating efficacy.

Main Methods:

• BHAPI was exposed to oxidation products of catecholamines (isoprenaline, epinephrine) and ROS.
• The conversion of BHAPI to HAPI and its iron-chelating activity were assessed.
• H9c2 cardiomyoblasts were treated with catecholamines, their oxidation products, and BHAPI/HAPI to evaluate cellular protection against ROS, glutathione depletion, and toxicity.

Main Results:

• BHAPI was effectively converted to the active iron chelator HAPI by ROS generated from catecholamine oxidation products.
• HAPI demonstrated strong iron-binding capacity, inhibiting hydroxyl radical generation.
• Both BHAPI and HAPI significantly protected H9c2 cells against catecholamine-induced oxidative stress, ROS formation, glutathione depletion, and toxicity.

Conclusions:

• BHAPI and its active form HAPI are effective in protecting cardiac cells against catecholamine-induced cardiotoxicity.
• This prochelator approach mitigates oxidative damage by inhibiting catecholamine oxidation and preventing ROS-mediated toxicity.
• BHAPI represents a promising therapeutic strategy for conditions involving oxidative stress and catecholamine toxicity.