Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach...

Area of Science:

• Radiochemistry
• Toxicology
• Pharmacology

Background:

• Radioactive cobalt (Co3O4) particles are poorly soluble and retained long-term in lungs after inhalation.
• Reducing retention time is critical to minimize radiation-induced lung damage.
• Enhancing cobalt dissolution promotes its elimination via urinary excretion.

Purpose of the Study:

• To evaluate ascorbic acid and chelating agents (DTPA, DFOB, EDTA) for enhancing radioactive cobalt particle dissolution.
• To assess the effect of these agents on the translocation of dissolved cobalt across an epithelial barrier.
• To identify improved decorporation strategies for radioactive cobalt intake.

Main Methods:

• Exposure of differentiated THP-1 macrophage-like cells and Calu-3 lung epithelial cells to cobalt particles and selected molecules.
• Culturing cells in a bicameral system to model the lung epithelial barrier.
• Measuring cobalt particle dissolution and translocation over a 7-day period.

Main Results:

• Ascorbic acid significantly increased Co3O4 particle dissolution.
• Combinations of ascorbic acid with DTPA and EDTA showed enhanced intracellular particle dissolution.
• DTPA alone had no effect; DFOB did not enhance dissolution.
• Most treatments did not significantly alter dissolved cobalt translocation across the epithelial barrier.

Conclusions:

• Ascorbic acid is a promising agent for enhancing radioactive cobalt particle dissolution.
• Combined therapy with ascorbic acid and chelating agents (DTPA, EDTA) may offer improved decorporation efficacy.
• Further research into decorporation strategies for radioactive cobalt inhalation is warranted.