Fluoride Action Network



  • Uranium and fluoride induce an adaptive response in mice exposed chronically.
  • Apoptosis regulation is involved in uranium-induced adaptive response.
  • Inflammatory control is involved in fluoride-induced adaptive response.
  • Uranium induces UPR and autophagy in the kidney.
  • Fluoride induces UPR in the kidney.


Despite their differences in physicochemical properties, both uranium (U) and fluoride (F) are nephrotoxicants at high doses but their adverse effects at low doses are still the subject of debate.


This study aims to improve the knowledge of the biological mechanisms involved through an adaptive response model of C57BL/6 J mice chronically exposed to low priming doses of U (0, 10, 20 and 40 mg/L) or F (0, 15, 30 and 50 mg/L) and then challenged with acute exposure of 5 mg/kg U or 7.5 mg/kg NaF.


We showed that an adaptive response occurred with priming exposures to 20 mg/L U and 50 mg/L F, with decreased levels of the biomarkers KIM-1 and CLU compared to those in animals that received the challenge dose only (positive control). The adaptive mechanisms involved a decrease in caspase 3/7 activities in animals exposed to 20 mg/L U and a decrease in in situ VCAM expression in mice exposed to 50 mg/L F. However, autophagy and the UPR were induced independently of priming exposure to U or F and could not be identified as adaptive mechanisms to U or F.


Taken together, these results allow us to identify renal adaptive responses to U and F at doses of 20 and 50 mg/L, probably through decrease apoptosis and inflammatory cell recruitment.

Graphical abstract



CLU clusterin
F fluoride
KIM-1 kidney injury molecule-1
U uranium
UN uranyl nitrate
UPR unfolded protein response
NMDR non-monotonic dose-response


Uranyl Fluoride; Kidney; Adaptation; Apoptosis; Inflammation