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Chronic Fluoride Ingestion Decreases 45Ca Uptake by Rat Kidney Membranes

1999; Elsevier BV; Volume: 129; Issue: 6 Linguagem: Inglês

10.1093/jn/129.6.1209

1541-6100

James L. Borke, Gary M. Whitford,

Arsenic contamination and mitigation

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 45Ca 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 μmol/L, respectively. ATP-dependent 45Ca 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.