title: Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects.
abstract: Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (~)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.
authors.affiliation: metanomics GmbH, Tegeler Weg 33, 10589 Berlin, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Bordag
authors.affiliation: Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Klie
authors.affiliation: Institute for Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Jürchott
authors.affiliation: Institute for Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Vierheller
authors.affiliation: Metanomics Health GmbH, Tegeler Weg 33, 10589 Berlin, Germany.
authors.forename: Hajo
authors.initials: H
authors.lastname: Schiewe
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr.15, 81377 Munich, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Albrecht
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr.15, 81377 Munich, Germany.
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr.15, 81377 Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr.15, 81377 Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schichor
authors.affiliation: Institute for Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Selbig
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D000077402:Pantoprazole; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D005938:Glucocorticoids; D003907:Dexamethasone; D000077402:Pantoprazole