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

Anne van der Meeren 1 Karine Devilliers 1 Sylvie Coudert 1 Agnès Moureau 1 Martine Defrance 1 Catherine Berthomieu 2 Véronique Malard 2 
2 IPM - Interactions Protéine Métal
BIAM - Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) : DRF/BIAM
Abstract : Following accidental inhalation of radioactive cobalt particles, the poorly soluble and highly radioactive Co3O4 particles are retained for long periods in lungs. To decrease their retention time is of crucial importance to minimize radiation-induced damage. As dissolved cobalt is quickly transferred to blood and eliminated by urinary excretion, enhancing the dissolution of particles would favor 60Co elimination. We evaluated the ability of ascorbic acid alone or associated with the chelating agents DTPA1, DFOB2 or EDTA3 to enhance dissolution of cobalt particles after macrophage engulfment, and the drug effects on the translocation of the soluble species CoCl2 through an epithelial barrier. We exposed differentiated THP-1 macrophage-like cells and Calu-3 lung epithelial cells cultured in a bicameral system to cobalt and selected molecules up to 7 days. DTPA, the recommended treatment in man, used alone showed no effect, whereas ascorbic acid significantly increased dissolution of Co3O4 particles. An additional efficacy in intracellular particles dissolution was observed for combinations of ascorbic acid with DTPA and EDTA. Except for DFOB, treatments did not significantly modify translocation of dissolved cobalt across the epithelial lung barrier. Our study provides new insights for decorporating strategies following radioactive cobalt particle intake.
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https://hal.archives-ouvertes.fr/hal-03749151
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Submitted on : Wednesday, August 10, 2022 - 2:21:31 PM
Last modification on : Thursday, August 11, 2022 - 3:32:13 AM

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Anne van der Meeren, Karine Devilliers, Sylvie Coudert, Agnès Moureau, Martine Defrance, et al.. Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention. Toxicology in Vitro, Elsevier, 2022, 84, pp.105448. ⟨10.1016/j.tiv.2022.105448⟩. ⟨hal-03749151⟩

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