engleski

Kinetics of uptake and elimination of complex drug mixture in zebrafish (Danio rerio)

Active pharmaceutical ingredients (APIs) belong to the most frequently detected categories of emerging environmental contaminants in the aquatic environment. However, in contrast to the large number of reports dealing with the occurrence and fate of APIs in abiotic environmental matrices, data on their concentrations in aquatic organisms are still relatively scarce. In this context, it is essential to understand and assess their bioconcentration potential as well as the uptake and elimination kinetics of APIs at realistic conditions, including environmentally relevant concentration levels and simultaneous exposure to complex mixtures of APIs. In this work, bioconcentration and elimination of 20 different APIs, covering a wide range of therapeutic categories and physicochemical properties, were studied under controlled laboratory conditions using zebrafish (Danio rerio) as a model organism. The exposure was performed at a concentration of 10 µg/L of each API in the mixture and involved a 7-day uptake period followed by a 7-day purification period. Samples of fish and water were collected daily and analyzed using a thoroughly validated multiresidue LC/MS methodology for both matrices, which allowed sensitive and accurate determination of APIs and their biotransformation products. To verify the pre-set exposure concentrations, water samples were processed immediately, while whole fish samples were frozen using liquid nitrogen, cryo- grinded, and stored at -80 ˚C until analysis. The results showed that the kinetics of API uptake was relatively fast, reaching a plateau for most of the APIs within 7 days. However, the bioconcentration factors of selected target APIs varied in a rather wide range. The most pronounced bioconcentration was observed for sertraline, oxazepam, and desloratadine with bioconcentration factors (BCF) reaching 55, 22, and 15, respectively. The bioconcentration of APIs was associated with a slight to moderate increase in CYP1A and CYP3A activity in API-exposed fish. The elimination of APIs, after 7 days of exposure was also relatively fast and reached rather low levels (≤ 5% of the maximum) within the first 2-3 days. The exception was azithromycin, caffeine, and desloratadine whose residual concentrations on the 7th day were around 27%, 18%, and 7%, respectively.

zebrafish ; pharmaceuticals ; bioaccumulation ; kinetics

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