無機フッ素による家兎腎障害に関する実験的研究

Some of the halogenated inhalation anesthetics are metabolized partly in the liver to produce inorganic fluoride, and serum inorganic fluoride in continuous high concentration may cause renal dysfunction. In this study, the influence of elevated serum inorganic fluoride concentration and the duration of its action on renal function were studied by continuous infusion of sodium fluoride in rabbits for 24hours. The rabbits were divided into Control (group C), Low dose (group L) and High dose (group H) groups with mean serum inoganic fluoride levels of 1.9 μ M, 62.4 μ M and 237.7μ M, respectively. Twinty-four hour total urine volume increased in group H compared to group C. Urinary excretion of β2-microgloblin (β(2)MG), leucine aminopeptidase (LAP) and N-acetyl-β-D-glucosaminidase (NAG), collected every 6 hours, increased significantly in group H within 0～6 hours, whereas LAP increased within 18～24 hours and NAG within 12～18 hours in group L, compared to group C. The area under the curve of serum inorganic fluoride concentration, when the increase of NAG (the earliest among β(2)MG, LAP and NAG) excretion was detected (6 hours in group H, 18 hours in group L), were similar (group H ; 1272±165 μ M・hours, group L ; 1197±189 μ M・hours). Free water clearance over 24 hours increased significantly in group H only. Morphological examination showed the absence of the brush border and that cellular damage had occurred in the renal tubules in both group L and group H. These findings were more apparent in group H. In conclusion, it was revealed that not only the elevated serum inorganic fluoride concentration but also its duration were the factors inducing renal dysfunction, beginning with proximal tubuar damage and subsequently developing to decreased water reabsorption.

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