title: Effect of NSAIDs and diuretics on nephrogenesis in an ex vivo embryogenic kidney model.
abstract: The kidney is one of the key organs in clearing foreign compounds. The effects of drugs on the developing kidney are relatively unknown. We studied the direct effect of furosemide, hydrochlorothiazide, ibuprofen, and indomethacin on kidney development in an ex vivo embryonic kidney model. At embryonic day 13, metanephroi were dissected from mice and cultured in control media or media supplemented with various clinically relevant concentrations of drugs. The ureteric tree was visualized by whole-mount staining and branching was evaluated by counting. Additionally, gene expression levels of Wt1, Sox9, Bmp7, Fgf8, and Gdnf were investigated. No distinct differences were noted on either ureteric tip development or gene expression analysis for each drug after 24 hr of exposure. Even though short-term exposure to clinically relevant concentrations seems not to disturb renal development, future research is needed to study prolonged or repeated exposures.
authors.affiliation: Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ruud Rg
authors.initials: RR
authors.lastname: Bueters
authors.forename: Annelies
authors.initials: A
authors.lastname: Klaasen
authors.forename: Lambertus P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Michiel F
authors.initials: MF
authors.lastname: Schreuder
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000096:biosynthesis; D005665:Furosemide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000196:embryology*; D051379:Mice; D008813:Mice, Inbred ICR; D009924:Organ Culture Techniques; D011247:Pregnancy; D055758:SOX9 Transcription Factor / Q000096:biosynthesis; D025721:WT1 Proteins / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D055419:Bone Morphogenetic Protein 7; D004232:Diuretics; C496457:Fgf8 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D025721:WT1 Proteins; C525820:bmp7 protein, mouse; D006852:Hydrochlorothiazide; D051524:Fibroblast Growth Factor 8; D005665:Furosemide; D007052:Ibuprofen; D007213:Indomethacin
keywords: NSAID; diuretics; embryonic kidney model; kidney development; nephrogenesis; toxicology