Dataset Information

Effect of β-adrenergic receptor antagonist and agonist on cardiac structure and function and whole body gene expression in Daphnia magna

ABSTRACT: Propranolol (PRO), a human β-AR (β-adrenergic receptor) antagonist, is considered to result in specific effects in a non-target species, D. magna, based on our previous studies. The present study investigated the effects of β-AR agents, including an antagonist and agonist using pharmacologically relevant endpoints as well as a more holistic gene expression approach to reveal the impacts and potential mode of actions (MOAs) in the model non-target species. Results show that the responses in cardiac endpoints and gene expression in D. magna are partially similar but distinguishable from the observations in different organisms. No effect was observed on heart size growth in PRO and isoprenaline (ISO) exposure. The contraction capacity of the heart was decreased in ISO exposure, and the heart rate was decreased in PRO exposure. Time-series exposures showed different magnitudes of effect on heart rate and gene expression dependent on the type of chemical exposure. Significant enrichment of gene families involved in protein metabolism and biotransformation was observed within the differentially expressed genes, and we also observed differential expression in juvenile hormone-inducible proteins in ISO and PRO exposure, which is suspected of having endocrine disruption potential. Taken together, deviation between the effects of PRO and ISO in D. magna and other organisms suggests dissimilarity in MOAs or attributes of target bio-molecules between species. Additionally, PRO and ISO may act as endocrine disruptors based on the gene expression observation. Results in the present study confirm that it is challenging to predict ecological impact of active pharmaceutical ingredients (APIs) based on the available data acquired through human-focused studies. Furthermore, the present study provided unique data and a case study on the impact of APIs in a non-target organism.

ORGANISM(S): Daphnia magna

PROVIDER: GSE104487 | GEO | 2018/04/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Hormesis is a dose response phenomenon characterized by a stimulation of an organismal response at low doses of a chemical and inhibition of the response (toxicity) at a higher dose. In the present study, Daphnia magna were exposed to the energetic compound 2,4,6-trinitrotoluene (TNT) for 21 days, and the endpoints survival, growth (length and dry weight), and reproduction (number of neonates per survivor) were assesed, identifying hormetic responses at the lower treatment levels. In order to elucidate the mechanisms leading to hormesis, microarray analysis was performed at 0.004 (hormetic), 0.12 (sometimes hormetic), and 1.85 (toxic) mg/L TNT. Functional and transcriptional benchmark dose analyses performed on differentially expressed genes suggested the involvement of lipid metabolism in hormetic responses and subsequently lipidomic analysis was performed on the same treatments. Lipid analysis supported the hypothesis that TNT exposure affected lipid metabolism, and showed that hormetic effects could be related to increases in some polyunsaturated fatty acids and ecosanoids known to be involved in Daphnia growth and reproduction. Chronic toxicity tests was designed to identify the hormetic range of D. magna responses to TNT. Daphnia magna younger than 24 h old and obtained from in-house cultures at the U.S. Army Engineer Research and Development Center, Environmental Laboratory (Vicksburg, MS) were used to initiate the bioassay. The experimental design consisted of one D. magna per test chamber and 10 test chambers per treatment level. In the microarray mass exposure, nominal treatment levels were 0.004, 0.02, 0.12, 0.44, and 1.85 mg/L. Based on the results of the testing in the 50 ml beakers, organisms from three treatments were selected for analysis of gene expression: 0.004, 0.12, and 1.85 mg/L. These treatments were selected to represent a hormetic concentration (0.004 mg/L), a toxic concentration (1.85 mg/L), and an intermediate concentration (0.12 mg/L). A total of 23 arrays used, with 5-6 replicates per each dose (solvent control, 0.004 mg/L, 0.12 mg/L, and 1.85 mg/L).

Dataset Information

Effect of β-adrenergic receptor antagonist and agonist on cardiac structure and function and whole body gene expression in Daphnia magna

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets