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Waterborne beclomethasone dipropionate affects the physiology of fish while its metabolite beclomethasone is not taken up

Journal article
Authors Bethanie Carney Almroth
Lina-Maria Gunnarsson
Filip Cuklev Stern
Fick Jerker
Erik Kristiansson
D. G. Joakim Larsson
Published in Science of the Total Environment
Volume 511
Pages 37-46
ISSN 0048-9697
Publication year 2015
Published at Institute of Neuroscience and Physiology
Department of Mathematical Sciences, Mathematical Statistics
Core Facilities, Genomics
Institute of Biomedicine, Department of Infectious Medicine
Pages 37-46
Language en
Links http://dx.doi.org/10.1016/j.scitot...
Keywords Beclomethasone dipropionate, Rainbow trout, Environmental risk assessment, Gene expression, Asthma medicine, Glucocorticoid
Subject categories Biological Sciences, Toxicology, Zoology

Abstract

Asthma is commonly treated with inhalable glucocorticosteroids, including beclomethasone dipropionate (BDP). This is a synthetic prodrug which is metabolized to the more active monopropionate (BMP) and free beclomethasone in humans. To evaluate potential effects of residual drugs on fish, we conducted a 14 day flow-through exposure experiment with BDP and beclomethasone using rainbow trout, and analyzed effects on plasma glucose, hepatic glutathione and catalase activity together with water and body concentrations of the BDP, BMP and beclomethasone. We also analyzed hepatic gene expression in BDP-exposed fish by microarray and quantitative PCR. Beclomethasone (up to 0.65 μg/L) was not taken up in the fish while BDP (0.65 and 0.07 μg/L) resulted in accumulation of both beclomethasone, BMP and BDP in plasma, reaching levels up to those found in humans during therapy. Accordingly, exposure to 0.65 μg/L of BDP significantly increased blood glucose as well as oxidized glutathione levels and catalase activity in the liver. Exposure to beclomethasone or the low concentration of BDP had no effect on these endpoints. Both exposure concentrations of BDP resulted in significantly higher transcript abundance of phosphoenolpyruvate carboxykinase involved in gluconeogenesis, and of genes involved in immune responses. As only the rapidly metabolized prodrug was potent in fish, the environmental risks associated with the use of BDP are probably small. However, the observed physiological effects in fish of BDP at plasma concentrations known to affect human physiology provides valuable input to the development of read-across approaches in the identification of pharmaceuticals of environmental concern.

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