RT Journal Article
SR Electronic
T1 STRAIN DIFFERENCES IN METABOLISM AND SUSCEPTIBILITY TO THE NEPHROTOXIC EFFECTS OF METHOXYFLURANE IN RATS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 481
OP 488
VO 184
IS 2
A1 RICHARD I. MAZZE
A1 MICHAEL J. COUSINS
A1 JON C. KOSEK
YR 1973
UL http://jpet.aspetjournals.org/content/184/2/481.abstract
AB Renal insufficiency due to metabolism of methoxyflurane to inorganic fluoride has been reported in man; however, an animal model has not been available. Therefore, the metabolism of methoxyflurane to inorganic fluoride and the renal effects of this metabolite were studied in adult male Fischer 344, Buffalo, Wistar, Sprague-Dawley and Long-Evans rats anesthetized with 0.5% methoxyflurane for three hours. Fischer 344 and Buffalo rats metabolized methoxyflurane to a greater extent than the other three strains, as evidenced by higher serum and urine inorganic fluoride activity. However, only Fischer 344 rats developed biochemical and pathological evidence of a renal lesion. Injection of identical doses of inorganic fluoride (NaF) produced a much greater degree of renal insufficiency in Fischer 344 rats than in Buffalo rats. It is concluded that there is variation in the rate of metabolism of methoxyflurane to inorganic fluoride and in its nephrotoxic effects among various rat strains. A high rate of methoxyflurane metabolism and increased susceptibility to the nephrotoxic effects of inorganic fluoride result in polyuric renal insufficiency in Fischer 344 rats. © 1973 by The Williams & Wilkins Co.