title: Fluoride ion toxicity in rabbit kidney thick ascending limb cells.
abstract: OBJECTIVE
  Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. We investigated the mechanisms of fluoride toxicity on an immortalized cell line.
  
  
  METHODS
  Cells were cultured for 2, 6 or 24 h in the presence of fluoride. Toxicity evaluation was based on: cell numbers, protein content, leucine-incorporation, lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) releases, Na-K-ATPase and Na-K-2Cl activities, electron microscope studies. Infrared analysis and fluoride microdetermination allowed crystal components.
  
  
  RESULTS
  At 5 mmol after 24 h, fluoride decreased cell numbers (-14%, *P < 0.05), protein content (-16%*), leucine incorporation (-54%*), Na-K-2Cl activity (-84%*), increased LDH (+145%*) and NAG release (+190%*). Na-K-ATPase was more sensitive and impaired from 1 mmol for 24h and after 2 h at 5 mmol. Crystal formation in mitochondria occurred after 6 h at 5 mmol. Infra-red analysis and fluoride microdetermination established that crystals contained sodium, phosphate and fluoride.
  
  
  CONCLUSIONS
  The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle's loop.
authors.affiliation: Département d'Anesthésie-Réanimation, Hĵpital Pitié-Salpêtrière, Paris, France. marie-laure.cittanova@psl.ap-hop-paris.fr
authors.forename: M L
authors.initials: ML
authors.lastname: Cittanova
authors.forename: L
authors.initials: L
authors.lastname: Estepa
authors.forename: R
authors.initials: R
authors.lastname: Bourbouze
authors.forename: O
authors.initials: O
authors.lastname: Blanc
authors.forename: M C
authors.initials: MC
authors.lastname: Verpont
authors.forename: E
authors.initials: E
authors.lastname: Wahbe
authors.forename: P
authors.initials: P
authors.lastname: Coriat
authors.forename: M
authors.initials: M
authors.lastname: Daudon
authors.forename: P M
authors.initials: PM
authors.lastname: Ronco
mesh_terms: D000118:Acetylglucosaminidase / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology / Q000633:toxicity*; D008138:Loop of Henle / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects*; D008854:Microscopy, Electron; D011817:Rabbits; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects*; D014463:Ultrasonography
chemical_list: D018685:Anesthetics, Inhalation; D028021:Sodium-Potassium-Chloride Symporters; D000118:Acetylglucosaminidase; D005459:Fluorides