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In Vivo Comparison of the Phenotypic Aspects and Molecular Mechanisms of Two Nephrotoxic Agents, Sodium Fluoride and Uranyl Nitrate

1
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SESANE/LRTOX, 92262 Fontenay-aux-Roses, France
2
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Toxicología, Av. IPN No. 2508 Col., San Pedro Zacatenco, México City, CP 07360, Mexico
3
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SESANE/LRSI, 92262 Fontenay-aux-Roses, France
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2019, 16(7), 1136; https://doi.org/10.3390/ijerph16071136
Received: 20 February 2019 / Revised: 22 March 2019 / Accepted: 26 March 2019 / Published: 29 March 2019
(This article belongs to the Special Issue The Harmful Effects of Fluoride Exposure)
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Abstract

Because of their nephrotoxicity and presence in the environment, uranium (U) and fluoride (F) represent risks to the global population. There is a general lack of knowledge regarding the mechanisms of U and F nephrotoxicity and the underlying molecular pathways. The present study aims to compare the threshold of the appearance of renal impairment and to study apoptosis and inflammation as mechanisms of nephrotoxicity. C57BL/6J male mice were intraperitoneally treated with a single dose of U (0, 2, 4 and 5 mg/kg) or F (0, 2, 5, 7.5 and 10 mg/kg) and euthanized 72 h after. Renal phenotypic characteristics and biological mechanisms were evaluated by urine biochemistry, gene/protein expression, enzyme activity, and (immuno)histological analyses. U and F exposures induced nephrotoxicity in a dose-dependent manner, and the highest concentrations induced severe histopathological alterations as well as increased gene expression and urinary excretion of nephrotoxicity biomarkers. KIM-1 gene expression was induced starting at 2 mg/kg U and 7.5 mg/kg F, and this increase in expression was confirmed through in situ detection of this biomarker of nephrotoxicity. Both treatments induced inflammation as evidenced by cell adhesion molecule expression and in situ levels, whereas caspase 3/7-dependent apoptosis was increased only after U treatment. Overall, a single dose of F or U induced histopathologic evidence of nephrotoxicity renal impairment and inflammation in mice with thresholds under 7.5 mg/kg and 4 mg/kg, respectively. View Full-Text
Keywords: uranium; fluoride; kidney; KIM-1; apoptosis; inflammation uranium; fluoride; kidney; KIM-1; apoptosis; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Bontemps, A.; Conquet, L.; Elie, C.; Magneron, V.; Gloaguen, C.; Kereselidze, D.; Tack, K.; Barbier, O.C.; Guéguen, Y. In Vivo Comparison of the Phenotypic Aspects and Molecular Mechanisms of Two Nephrotoxic Agents, Sodium Fluoride and Uranyl Nitrate. Int. J. Environ. Res. Public Health 2019, 16, 1136.

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