Fluoride Nephropathy: Lack of Direct Involvement of Renal ATPase

Author:

Tobin Thomas,Akera Tai,Dworin Jeffrey Z.,Brody Theodore M.

Abstract

A dose-related fluoride- or methoxyflurane-dependent nephropathy has been demonstrated in Fisher 344 rats, which appears related to methoxyflurane nephropathy in man. Since the fluoride ion inhibits Na++K4 ATPase, the possibility of direct involvement of renal ATPase in this syndrome was investigated. Fluoride inhibited rat kidney Na++K4 ATPase in vitro in the presence of Na+ and ATP and the inhibition produced in this way was stable under conditions used for preparation of this enzyme. However, when sodium fluoride was given subcutaneously to Fisher 344 rats their urinary output increased fivefold without any significant changes in renal Na++K4-ATPase or Mg2+-ATPase activity. These results appear to rule out a direct irreversible action of fluoride on renal Na++K4-ATPase or Mg2+-ATPase activity as a mechanism of fluoride or methoxyflurane nephropathy. An indirect action of fluoride on Na+ transport by limiting the supply of glycolytic energy to the pump remains likely.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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