Bone antiresorptives as potential chelators for iron overload diseases

Area of Science:

• Pharmacology
• Biochemistry
• Toxicology

Background:

• Iron overload diseases (IOD) cause significant health issues, and current treatments have adverse effects.
• Drug repositioning (DR) offers a strategy to find new uses for existing medications.
• Antiresorptives (AR) are drugs used to inhibit bone resorption.

Purpose of the Study:

• To investigate the iron-binding and antioxidant potential of specific antiresorptives (bisphosphonates and strontium ranelate).
• To evaluate their efficacy as alternative treatments for iron overload diseases, independent of bone conditions.

Main Methods:

• Competition equilibrium tests were performed using bisphosphonates with ferric calcein and ferric transferrin.
• Antioxidant activity was assessed against iron-induced reactive species generation, with and without ascorbate.
• Cell models were used to evaluate the protective effects against iron-dependent oxidative stress, considering calcium's influence.

Main Results:

• Bisphosphonates demonstrated a moderate capacity for iron scavenging.
• These drugs exhibited antioxidant activity against iron-induced oxidative stress.
• Etidronate and tiludronate effectively protected cells from iron-dependent oxidative damage.
• Physiological calcium levels did not negate the chelating and antioxidant properties of the bisphosphonates.

Conclusions:

• Etidronate and tiludronate possess favorable physicochemical properties for iron chelation and antioxidant activity.
• These findings suggest their potential utility in a drug repositioning strategy for treating iron overload diseases.