Nutrient Interactions and Toxicity Chronic Fluoride Ingestion Decreases Ca Uptake by Rat Kidney Membranes

High exposures to fluoride (F) may occur in environments rich in F from natural or industrial sources and from misuse of F-containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F ingestion on ATP-dependent Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F alters Ca transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F (0.9 mg/L), semi-purified diet with a Ca concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F levels of ,0.4, 2, 7, or 35 mmol/L, respectively. ATP-dependent Ca uptake was significantly lower in the 150 mg F/L exposure group than in the 0 mg F/L controls (P , 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca-pump (P , 0.05, 150 mg F/L group versus control) and endoplasmic reticulum Ca-pump (P , 0.05 for both the 50 and 150 mg F/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca-pump antibodies showed less (P , 0.05) endoplasmic reticulum Ca-pump protein and plasma membrane Ca-pump protein in all treatment groups than controls. Both Ca-pumps are transport molecules of great importance in the regulation of Ca homeostasis. Our study suggests that chronic, high F ingestion producing high plasma F levels may occur in humans and may affect Ca homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca-pump proteins. J. Nutr. 129: 1209–1213, 1999.