Bone antiresorptives as potential chelators for iron overload diseases.

Iron overload diseases (IOD) are harmful conditions that may lead to a significant decrease in quality of life. The only three IOD approved chelators have significant adverse effects that hinder therapeutic adherence. The search for new chelators may benefit from drug repositioning (DR), a strategy that aims to identify new applications for approved drugs. Antiresorptives (AR) are drugs that inhibit bone resorption. Here, the iron binding and antioxidant effects of four bisphosphonates (etidronate, alendronate, tiludronate, and zoledronate) and strontium ranelate AR were studied in buffer and cell models, in order to verify their potential as alternative treatments of IOD in the absence of bone disease. Competition equilibrium tests between the bisphosphonates and ferric calcein or ferric transferrin showed a moderate ability to scavenge iron. Bisphosphonates showed antioxidant activity against iron-induced reactive species generation in the presence of ascorbate. Etidronate and tiludronate helped to prevent cell death by iron-dependent oxidative stress. Although measurable, the effect of physiological levels of calcium did not prevent the desired chelating and antioxidant effects of the bisphosphonates. Our results show that etidronate and tiludronate have valuable physicochemical properties that could be employed in a DR strategy for the treatment of IOD.