Effects of Acute Sodium Fluoride Exposure on Kidney Function, Water Homeostasis, and Renal Handling of Calcium and Inorganic Phosphate Mitzi Paola Santoyo-Sanchez & Maria del Carmen Silva-Lucero & Laura Arreola-Mendoza & Olivier Christophe Barbier Received: 1 October 2012 / Accepted: 27 January 2013 / Published online: 12 February 2013 # Springer Science+Business Media New York 2013 Abstract Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concen- tration of 0.625 μg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney par- ticipates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations. Keywords Fluoride . Kidney . Acute exposure . Calcium . Phosphate . Proteinuria . Diuresis Introduction Fluorine is a highly electronegative and reactive element and therefore never naturally occurs in a free state. Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. The main source of fluoride exposure is through the intake of ground- water contaminated with the inorganic form of this mineral (reaching concentrations of 30–50 mg/l), mainly from geo- logical sources. Currently, there is no consensus about the role of fluoride as an essential element. However, low doses of fluoride prevent dental caries, thus justifying water fluo- ridation programs (at 1.0 mg/l) and topical applications through toothpastes and gels. The negative effects associat- ed with fluoride exposure include dental fluorosis in pop- ulations chronically exposed to relatively low doses of inorganic fluoride in potable water (1.0–2.0 mg/l) and skel- etal fluorosis upon exposure to higher levels; these effects are related to an alteration in calcium homeostasis [1]. Further, fluoride induces toxic effects in other target organs such as the liver and kidney. It is known that approximately 50–80 % of the fluoride absorbed is excreted through the urine, primarily by glomerular filtration. The results of some previous studies have suggested that environmental or oc- cupational fluoride exposure is associated with renal dam- age [2]. However, it is known that renal toxicity could be a consequence of acute or chronic fluoride exposure in both animals and humans [3]. Subsequent studies have highlight- ed the presence of fluoride in drinking water as a possible contributor to the etiology of chronic kidney disease [4]. In the nephron, the main target of fluoride is the proximal tubule epithelial cell [5, 6]. Recently, two proximal tubule- M. P. Santoyo-Sanchez : M. del Carmen Silva-Lucero : O. C. Barbier (*) Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN No. 2508 Col, San Pedro Zacatenco, Mexico City, CP 07360, Mexico e-mail: obarbier@cinvestav.mx L. Arreola-Mendoza Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y Desarrollo del Instituto Politécnico Nacional (CIIEMAD-IPN), San Pedro Zacatenco, Mexico City, Mexico Biol Trace Elem Res (2013) 152:367–372 DOI 10.1007/s12011-013-9622-y