Abstract
Treatment of Fischer 344 rats with phenobarbital prior to a low dose of methoxyflurane resulted in increased excretion of the methoxyflurane metabolites, inorganic fluoride and oxalic acid, increased urine flow rate and a greater degree of mitochondrial swelling in renal proximal convoluted tubule cells compared to that observed in rats treated with methoxyflurane alone. Pretreatment with SKF 525-A decreased the metabolism of methoxyflurane and ameliorated its nephrotoxicity, confirming the association between methoxyflurane metabolism and nephrotoxicity. Injection of inorganic fluoride in an amount approximating that which results from methoxyflurane metabolism produced renal functional and morphological abnormalities which were similar to those produced by methoxyflurane anesthesia. Injection of oxalic acid in a dose similar to that resulting from methoxyflurane metabolism produced no abnormalities. Ten times this dose of oxalic acid caused anuric renal failure, with extensive renal tubular oxalate deposition, but without the ultrastructural changes characteristic of methoxyflurane nephropathy. These studies indicate that inorganic fluoride is responsible for the acute polyuric renal lesion which occurs after methoxyflurane administration.
Footnotes
- Received March 15, 1974.
- Accepted May 7, 1974.
- © 1974 by The Williams & Wilkins Co.
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