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Richard I. Mazze
Environmental Health Perspectives
Vol. 15 (Jun., 1976), pp. 111-119
Published by: The National Institute of Environmental Health Sciences
Stable URL: http://www.jstor.org/stable/3428393
Page Count: 9
You can always find the topics here!Topics: Fluorides, Nephrotoxicity, Anesthesia, Urine, Dosage, Metabolism, Toxicity, Polyuria, Anesthesiology, Animal models
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Investigations of methoxyflurane-induced nephrotoxicity in man have been extensively aided by the use of an animal model. To be of value the animal model must share similar metabolic pathways with man and have the same clinical manifestations of the disease process. The Fischer 344 rat appears to meet these criteria. The predominant factors in the production of methoxyflurane nephrotoxicity appear to be high methoxyflurane dosage and serum inorganic fluoride concentration. It is likely that secondary factors include: (1) a high rate of methoxyflurane metabolism and sepsitivity of the kidney to inorganic fluoride toxicity; (2) concurrent treatment with other nephrotoxic drugs; (3) preexisting renal disease; (4) surgery of the urogenital tract, aorta, or renal vasculative; (5) repeat administration of methoxyflurane due to accumulation of inorganic fluoride and, perhaps, methoxyflurane induction of its own metabolism: and (6) concurrent treatment with enzyme-inducing drugs such as phenobarbital.
Environmental Health Perspectives © 1976 The National Institute of Environmental Health Sciences