In vitro assessment of cobalt oxide particle dissolution in simulated lung fluids for identification of new decorporating agents

Inhalation of 60Co3O4 particles may occur at the work place in nuclear industry. Their low solubility may result in chronic lung exposure to γ rays. Our strategy for an improved therapeutic approach is to enhance particle dissolution to facilitate cobalt excretion, as the dissolved fraction is rapid...

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Bibliographic Details
Published in:	Toxicology in vitro Vol. 66; p. 104863
Main Authors:	Van Der Meeren, Anne, Lemaire, David, Coudert, Sylvie, Drouet, Guillaume, Benameur, Myriam, Gouzerh, Célia, Hee, Cien Yoong, Brunquet, Pauline, Trochaud, Bastien, Floriani, Magali, Gateau, Christelle, Lebrun, Colette, Delangle, Pascale, Berthomieu, Catherine, Malard, Véronique
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-08-2020 Elsevier Science Ltd Elsevier
Subjects:	Bioaccessibility Biochemistry Biochemistry, Molecular Biology Body Fluids Chelating Agents - chemistry Chelation Cobalt Cobalt - chemistry Cobalt oxide particles Cobalt oxides Cobalt Radioisotopes - chemistry Computer simulation Contamination Copper Decontamination - methods Destabilization Dissolution Dissolution and chelating agents Edetic Acid - chemistry In vitro Incubation Inhalation Iron Life Sciences Lung Lungs Manganese Metal oxides Oxides - chemistry Particulates Pentetic Acid - chemistry Redox potential Respiration Solubility Bioaccessibility Cobalt oxide particles Dissolution and chelating agents In vitro Lung
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Summary:	Inhalation of 60Co3O4 particles may occur at the work place in nuclear industry. Their low solubility may result in chronic lung exposure to γ rays. Our strategy for an improved therapeutic approach is to enhance particle dissolution to facilitate cobalt excretion, as the dissolved fraction is rapidly eliminated, mainly in urine. In vitro dissolution of Co3O4 particles was assessed with two complementary assays in lung fluid surrogates to mimic a pulmonary contamination scenario. Twenty-one molecules and eleven combinations were selected through an extensive search in the literature, based on dissolution studies of other metal oxides (Fe, Mn, Cu) and tested for dissolution enhancement of cobalt particles after 1–28 days of incubation. DTPA, the recommended treatment following cobalt contamination did not enhance 60Co3O4 particles dissolution when used alone. However, by combining molecules with different properties, such as redox potential and chelating ability, we greatly improved the efficacy of each drug used alone, leading for the highest efficacy, to a 2.7 fold increased dissolution as compared to controls. These results suggest that destabilization of the particle surface is an important initiating event for a good efficacy of chelating drugs, and open new perspectives for the identification of new therapeutic strategies. [Display omitted] •The low solubility of radioactive cobalt oxide particles contribute to the related-risk following inhalation•Increasing dissolution is the first step in the improvement of decorporation approaches.•DTPA, the recommended treatment following internal contamination with cobalt, has no effect on Co3O4 particle dissolution.•Molecules with complementary properties enhance Co3O4 particle dissolution in lung fluid surrogates.•Destabilization of particle surface is a prerequisite to the action of chelating agents and chelation of free cobalt ions.
ISSN:	0887-2333 1879-3177
DOI:	10.1016/j.tiv.2020.104863