Renal adaptive response to exposure to low doses of uranyl nitrate and sodium fluoride in mice,Journal of Trace Elements in Medicine and Biology

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Renal adaptive response to exposure to low doses of uranyl nitrate and sodium fluoride in mice
Journal of Trace Elements in Medicine and Biology ( IF 3.6 ) Pub Date : 2020-12-17 , DOI: 10.1016/j.jtemb.2020.126708
Alice Bontemps-Karcher ₁ , Victor Magneron ₁ , Laurine Conquet ₁ , Christelle Elie ₁ , Céline Gloaguen ₁ , Dimitri Kereselidze ₁ , Laurence Roy ₁ , Olivier C Barbier ₂ , Yann Guéguen ₁

Affiliation

Background

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. METHODS: 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.

Results

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.

Conclusion

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.

中文翻译：

小鼠暴露于低剂量硝酸铀酰和氟化钠的肾脏适应性反应

背景

尽管它们的物理化学性质不同，但铀 (U) 和氟化物 (F) 在高剂量时都是肾毒性物质，但它们在低剂量时的不良反应仍然存在争议。方法：本研究旨在通过 C57BL/6 J 小鼠长期暴露于低启动剂量的 U（0、10、20 和 40 mg/L）或 F（0， 15、30 和 50 mg/L），然后以 5 mg/kg U 或 7.5 mg/kg NaF 的急性暴露进行挑战。

结果

我们表明，与仅接受攻击剂量的动物（阳性对照）相比，20 mg/LU 和 50 mg/LF 的初始暴露发生了适应性反应，生物标志物 KIM-1 和 CLU 的水平降低。适应性机制涉及暴露于 20 mg/LU 的动物中 caspase 3/7 活性的降低和暴露于 50 mg/L F 的小鼠中原位VCAM 表达的降低。然而，自噬和 UPR 的诱导与引发暴露无关U 或 F 并且不能被识别为 U 或 F 的适应性机制。