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Fluoride ion toxicity in rabbit kidney thick ascending limb cells

Published online by Cambridge University Press:  16 August 2006

M. L. Cittanova ,
L. Estepa ,
R. Bourbouze ,
O. Blanc ,
M.-C. Verpont ,
F. Wahbe ,
P. Coriat ,
M. Daudon  and
P. M. Ronco
M. L. Cittanova
Affiliation:
Département d’Anesthésie-Réanimation, Hôpital Pitié-Salpêtriére, Paris, France
L. Estepa
Affiliation:
Service de Biochimie A, Hôpital Necker, Paris, France
R. Bourbouze
Affiliation:
Laboratoire de biochimie et de Glycobiologie, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France
O. Blanc
Affiliation:
Pharmacie, Hôpital Cochin
M.-C. Verpont
Affiliation:
INSERM U 64, Paris, France
F. Wahbe
Affiliation:
Laboratoire d’Explorations Fonctionnelles, Paris, France
P. Coriat
Affiliation:
Département d’Anesthésie-Réanimation, Hôpital Pitié-Salpêtriére, Paris, France
M. Daudon
Affiliation:
Service de Biochimie A, Hôpital Necker, Paris, France
P. M. Ronco
Affiliation:
Néphrologie, Hôpital Tenon, France
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Abstract

Background and 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-βglucosaminidase (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 24 h 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.

Keywords

drug toxicityfluorine compoundshydrofluoric acidfluorideskidneynephronskidney tubulesloop of henle
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 19 , Issue 5 , May 2002 , pp. 341 - 349
Copyright
2002 European Society of Anaesthesiology

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