Effect of Toxic Levels of Dietary Fluoride on Citrate Metabolism in the Rat

Citrate metabolism was studied in rats fed diets containing 450 or 600 ppm F. Ingestion on the high fluoride diet for 3 days caused an elevation of liver and blood citrate concentrations and a decrease in femur citrate content. After 2 weeks, liver and blood citrate concentrations returned to normal, and femur citrate remained depressed. The continuous intravenous infusion of 3 or 10 mg of citrate per day for 3 days did not cause an increase in either liver or blood citrate levels. The capacity of bone slices to incorporate 2-14C-acetate into citrate or total organic acids was not altered when the slices were prepared from rats fed the fluoride diet for 3 days. Oxidation of a tracer dose of 14C-citrate to 14CO2was not inhibited, nor were kidney citrate concentrations affected in rats fed the fluoride-containing diet for 3 days. Although the addition of 20 ppm F to an isolated, perfused rat liver caused changes in the concentrations of glycolytic intermediates, it did not alter citrate levels. The activities of rat liver aconitase, isocitrate dehydrogenase, malate dehydrogenase, citrate-cleavage enzyme, and citrate condensing enzyme were not directly affected by fluoride ingestion for 3 or 14 days. It was concluded that the elevation of liver and blood citrate observed in rats fed a fluoride-containing diet for 3 days was caused by a specific but as yet undetermined metabolic effect of fluoride. It cannot be exclusively the result of: 1) the fluoride-induced release of citrate from bone, 2) inhibited citrate oxidation, or 3) fluoride inhibition of liver citrate metabolizing enzymes.