Glucocorticoid activity detected by in vivo zebrafish assay and in vitro glucocorticoid receptor bioassay at environmental relevant concentrations

• Published in: Chemosphere (Oxford) Vol. 144; pp. 1162 - 1169
• Main Authors: Chen, Qiyu, Jia, Ai, Snyder, Shane A., Gong, Zhiyuan, Lam, Siew Hong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2016
• Subjects: Animals; Biological Assay; Dose-Response Relationship, Drug; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - metabolism; Environmental glucocorticoid contaminants; Environmental Monitoring - methods; Gene expression; Gene Expression - drug effects; Glucocorticoids - analysis; Glucocorticoids - pharmacology; In vitro glucocorticoid receptor bioassay; In vivo zebrafish assay; Larva - drug effects; Larva - genetics; Larva - metabolism; Liver - drug effects; Liver - metabolism; Male; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Transcriptional Activation; Waste Water - chemistry; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; In vitro glucocorticoid receptor bioassay; Environmental glucocorticoid contaminants; Gene expression; In vivo zebrafish assay
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2015.09.089

Glucocorticoids are pharmaceutical contaminants of emerging concern due to their incomplete removal during wastewater treatment, increased presence in aquatic environment and their biological potency. The zebrafish is a popular model for aquatic toxicology and environmental risk assessment. This study aimed to determine if glucocorticoids at environmental concentrations would perturb expression of selected glucocorticoid-responsive genes in zebrafish and to investigate their potentials as an in vivo zebrafish assay in complementing in vitro glucocorticoid receptor bioassay. The relative expression of eleven glucocorticoid-responsive genes in zebrafish larvae and liver of adult male zebrafish exposed to three representative glucocorticoids (dexamethasone, prednisolone and triamcinolone) was determined. The expression of pepck, baiap2 and pxr was up-regulated in zebrafish larvae and the expression of baiap2, pxr and mmp-2 was up-regulated in adult zebrafish exposed to glucocorticoids at concentrations equivalent to total glucocorticoids reported in environmental samples. The responsiveness of the specific genes were sufficiently robust in zebrafish larvae exposed to a complex environmental sample detected with in vitro glucocorticoid activity equivalent to 478 pM dexamethasone (DEX-EQ) and confirmed to contain low concentration (0.2 ng/L or less) of the targeted glucocorticoids, and possibly other glucocorticoid-active compounds. The findings provided in vivo relevance to the in vitro glucocorticoid activity and suggested that the environmental sample can perturb glucocorticoid-responsive genes in its original, or half the diluted, concentration as may be found in the environment. The study demonstrated the important complementary roles of in vivo zebrafish and in vitro bioassays coupled with analytical chemistry in monitoring environmental glucocorticoid contaminants. •Zebrafish genes are responsive to glucocorticoids at environmental concentrations.•Identified robust glucocorticoid-responsive genes for in vivo zebrafish assay.•In vivo and in vitro detection of glucocorticoid activity in environmental sample.•Analytical chemistry confirmed glucocorticoids in environmental sample.•Combined approaches useful for environmental glucocorticoid monitoring.