Kidney - Adverse Effects
Sodium fluoride
CAS No. 7681-49-4

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• Note: The following is a limited selection of abstracts from 1994 to present.
• Due to length, we present this as a separate section
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Kidney section for fluorine & organofluorine pesticides.
• When time allows more information will be added.

Wei Sheng Yan Jiu. 2005 May;34(3):287-8.

[The dose-effect relationship of water fluoride levels and renal damage in children]

[Article in Chinese]

Liu JL, Xia T, Yu YY, Sun XZ, Zhu Q, He W, Zhang M, Wang A.

Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

OBJECTIVE: To explore the dose-effect relationship of water fluoride levels and renal damage in children and observe the difference of renal function between high-loaded fluoride people and dental fluorosis people in the same water fluoride level region.
METHODS: 210 children were divided into seven groups in term of drinking water fluoride levels and whether they suffered from dental fluorosis. Fluoride concentrations in urine and serum and activities of urine NAG and gamma-GT were determined.
RESULTS: The urine and serum fluoride of high-loaded fluoride people and dental fluorosis people increased compared with control, moreover fluoride contents in urine and serum increased gradually with the increase of fluoride level in drinking water. Urine NAG and gamma-GT activities significantly increased in dental fluorosis people from area of 2.58 mg/L fluoride in drinking water and in those two groups from area of 4.51 mg/L fluoride in drinking water. Moreover, there existed an obvious dose-effect relationship between the drinking water fluoride concentration and NAG and gamma-GT activity.
CONCLUSION: Over 2.0 mg/L fluoride in drinking water can cause renal damage in children, and the damage degree increases with the dinking water fluoride content. Renal damage degree is not related to whether the children suffered from dental fluorosis and mainly due to water fluoride concentration.

PMID: 16111031 [PubMed - in process]

Toxicol Lett. 2005 Jul 22; [Epub ahead of print]

Proteomic analysis of kidney in fluoride-treated rat.

Xu H, Hu LS, Chang M, Jing L, Zhang XY, Li GS.

Institute of Endemic Disease, Jilin University, Changchun 130021, China.

The recent development of proteomic techniques has enabled investigators to directly examine the population of proteins present in biological systems. We first report here the proteomic changes of renal protein induced by fluoride. To investigate molecular mechanisms of renal injury induced by fluoride, proteins were isolated from rat kidney and profiled by two-dimensional gel electrophoresis (2DE). With the analysis of Image-Master 2D Elite software, 141 up-regulated and eight down-regulated protein spots in 2DE gels of fluoride-treated group were gained by comparison to the control group, 13 of which were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The identified proteins are mainly related with cell proliferation, metabolism and oxidative stress, and provide a valuable clue to explore the mechanism of renal fluorosis. This study also shows that the proteomic techniques were powerful in fluoride toxical field.

PMID: 16043314 [PubMed - as supplied by publisher]

Brain Research, 1998 Feb 16;784(1-2):284-98.

Chronic administration of aluminum-fluoride and sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity.

Varner JA, Jensen KF, Horvath W, Isaacson RL.

Psychology Department, Binghamton University, Binghamton, NY, USA..

This low-dose (1 ppm fluoride in deionized distilled drinking water) and long-term (52 weeks) rat study reported histological evidence of glomerular distortions and other signs of kidney disorders in animals in both the AlF3 and NaF groups. The Al levels in samples of brain and kidney were higher in both the AlF3 and NaF groups relative to controls

J Inorg Biochem 2003 Jan 15;93(3-4):243-6.

Substrate inhibition of rat liver and kidney arginase with fluoride

Tormanen CD.

Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48858, USA.

Abstract: Fluoride is an uncompetitive inhibitor of rat liver arginase. This study has shown that fluoride caused substrate inhibition of rat liver arginase at substrate concentrations above 4 mM. Rat kidney arginase was more sensitive to inhibition by fluoride than liver arginase. For both liver and kidney arginase preincubation with fluoride had no effect on the inhibition. When assayed with various concentrations of L-arginine, rat kidney arginase did not have Michaelis-Menten kinetics. Lineweaver-Burk and Eadie-Hofstee plots were nonlinear. Kidney arginase showed strong substrate activation at concentrations of L-arginine above 4 mM. Within narrow concentrations of L-arginine, the inhibition of kidney arginase by fluoride was uncompetitive. Fluoride caused substrate inhibition of kidney arginase at L-arginine concentrations above 1 mM. The presence of fluoride prevented the substrate activation of rat kidney arginase.

PMID: 12576287 [PubMed - indexed for MEDLINE]

Full report availavle at:

Fluoride 2002; 35(1):38-50.

Toxic effects of fluoride on rabbit kidney

A Shashi, JP Singh, SP Thapar.

Abstract: Summary: The purpose of this study was to assess renal damage in experimental fluorosis. Young albino rabbits were injected with 5, 10, 20, and 50 mg NaF/kg body weight/day for fifteen weeks and then sacrificed. No significant clinical signs of toxicity were found in animals exposed to the lowest dose. At the higher doses, however, the cytoachitecture of the kidneys exhibited increasing amounts of cloudy swellings, degeneration of tubular epithelia, tissue necrosis, extensive vacuolization in renal tubules, hypertrophy and atrophy of glomeruli, exudation, interstitial oedema, and interstitial nephritis. These changes in the kidneys result in impaired renal function in chronic fluoride intoxication.

Eur J Anaesthesiol 2002 May;19(5):341-9.

Fluoride ion toxicity in rabbit kidney thick ascending limb cells

Cittanova ML, Estepa L, Bourbouze R, Blanc O, Verpont MC, Wahbe E, Coriat P, Daudon M, Ronco PM.

Departement d'Anesthesie-Reanimation, Hjpital Pitie-Salpetriere, Paris, France.

BACKGROUND AND OBJECTIVE: Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. We investigated the mechanisms of fluoride toxicity on an immortalized cell line.
METHODS: Cells were cultured for 2, 6 or 24 h in the presence of fluoride. Toxicity evaluation was based on: cell numbers, protein content, leucine-incorporation, lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) releases, Na-K-ATPase and Na-K-2Cl activities, electron microscope studies. Infrared analysis and fluoride microdetermination allowed crystal components.
RESULTS: At 5 mmol after 24 h, fluoride decreased cell numbers (-14%, *P < 0.05), protein content (-16%*), leucine incorporation (-54%*), Na-K-2Cl activity (-84%*), increased LDH (+145%*) and NAG release (+190%*). Na-K-ATPase was more sensitive and impaired from 1 mmol for 24h and after 2 h at 5 mmol. Crystal formation in mitochondria occurred after 6 h at 5 mmol. Infra-red analysis and fluoride microdetermination established that crystals contained sodium, phosphate and fluoride.
CONCLUSIONS: The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle's loop.

New Zealand MAF Biosecurity Authority, Ministry of Agriculture and Forestry

Impact of a Volcanic Eruption on Agriculture and Forestry in New Zealand (2001)

... Experimental trials involving NaF intoxication showed that the principal signs of acute fluorosis were depression, salivation, hyperpnoea, nasal secretions, inappetance, blindness, ataxia, coma and death(6). The rumen, reticulum and abomasum showed epithelial necrosis and hyperaemia, oedema and haemorrhage in the lamina propria and submucosa. The kidneys showed necrosis of epithelial cells in the proximal convoluted tubules.

Full report available at:

Fluoride 2000; 33(4):210-217.

Acute renal damage dose response in rats to intravenous infustion of sodium fluoride

Tomotaro Dote, Koichi Kono, Kan Usuda, Hiroyuki Nishiura, Teruaki Tagawa.

Abstract: SUMMARY: Rapid acute renal injury in Wistar rats from fluoride (F) following single-dose NaF infusions of 0 mg F (control), 1 mg F (Group 1), 2 mg F (Group 2), and 3 mg F (Group 1) was assessed by examining three collections of bladder urine at 2-h intervals for six hours after the infusions. The urinary parameters investigated were: urine volume, excretion of F, creatinine, and -glutathione S-transferase (-GST), and the activity of N-acetyl- -D-glucosa-midase (NAG). Compared with the control, the urine volume increased (polyuria) in Group 1 but decreased in groups 2 and 3. F excretion increased in groups 1 and 2 but was lower in Group 3 than in Group 1. In Group 3, creatinine excretion decreased compared with the control, but the activities of -GST and NAG steadily increased in Group 3. The decreases in F and creatinine excretion in Group 3 are attributable to glomerular dysfunction, and the increases in -GST and NAG activities in Group 3 indicate acute proximal renal tube injury. The kidney toxicity of intravenous administration of NaF to laboratory rats was thus dose related, and an infusion of 3 mg F was sufficient to cause acute renal dysfunction.

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