Bioavailability of flumequine and diclofenac in mice exposed to a metal‐drug chemical cocktail. Evaluation of selenium protective role.

Abstract

Background and PurposeOrganisms, including humans, are subjected to the simultaneous action of a wide variety of pollutants, the effects of which should not be considered in isolation, as many synergies and antagonisms have been found between many of them. Therefore, this work proposes an in vivo study to evaluate the effect of certain metal contaminants on the bioavailability and metabolism of pharmacological active compounds. Since the most frequent entry vector is through ingestion, the influence of the gut microbiota and the possible protective effect of selenium has been additionally evaluated.Experimental approachIn this work, a controlled exposure experiment in mammals (Mus musculus) to a ‘chemical cocktail’ consisting of metals (arsenic, cadmium and mercury) and pharmaceuticals (diclofenac and flumequine) and in addition, the presence of selenium has been evaluated as an antagonist. Mice plasma samples were measured by UPLC coupled to quadrupole time of flight (QTOF) mass spectrometry detection. Analytical procedures were optimized and validated. A targeted search of 48 metabolites was also performed.Key ResultsThe bioavailability of flumequine, diclofenac and its hydroxymetabolites is discussed. Additionally, changes in some metabolic pathways are discussed.Conclusions & ImplicationsThe presence of metals and/or selenium in the mice diet as well as the previous treatment of mice with antibiotic mixture (Abxs), which deplete the gut microbiota and alters the gut epithelium capacity of metabolizing drugs due to the possession of a large carriage of Cytochrome P450 (CYP) enzymes, have been decisive on the bioavailability and metabolism of the tested pharmaceuticals.