Department of Genetics and Evolution, Center of Biological Sciences and the Health, Federal University of São Carlos, Washington Luis, km 235, 13560-970 São Carlos, São Paulo, Brazil.
Department of Biological Sciences, Bauru Dental School, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, 17012-901 Bauru, São Paulo, Brazil.
Toxicol Appl Pharmacol. 2018 Nov 1;358:68-75. doi: 10.1016/j.taap.2018.09.010. Epub 2018 Sep 11.
Fluoride (F) can induce changes in the expression of several liver proteins. It is suggested that these changes are dose- and time-dependent. The objective of this study was to analyze the effect of different F concentrations and exposure times to this ion on the pattern of protein expression in the liver of rats. Thirt-six 21-day-old male Wistar rats were divided into 2 groups (n = 18) according to the treatment duration (20 or 60 days). Each of these groups was then divided into 3 subgroups (n = 6) according to the concentration of F administered in drinking water, as follows: 0 mg/L (control), 15 mg/L or 50 mg/L. After the experiment periods, the animals were anesthetized and the liver and blood were collected. F was analyzed in plasma and liver. Part of the liver was fixed for histological analysis. Liver proteins were extracted and prepared for quantitative label-free mass spectrometry analysis. F concentrations in plasma and liver were significantly higher in the group treated with 50 mg /L in comparison with control, regardless the time of exposure. Histological alterations in the liver were more evident in the subgroups treated for 20 days. The proteomic analysis revealed changes in proteins related to endoplasmic reticulum and mitochondrial oxidative stress, mitochondrial alteration, apoptosis and cellular respiration upon exposure to F. The results reinforce previous findings showing that the effects of F in the liver are dose- and time-dependent and provide the molecular basis for understanding the evolution of these effects.
氟化物 (F) 可诱导几种肝脏蛋白的表达发生变化。据认为，这些变化是剂量和时间依赖性的。本研究的目的是分析不同 F 浓度和暴露时间对大鼠肝脏蛋白表达模式的影响。36 只 21 日龄雄性 Wistar 大鼠根据处理时间（20 或 60 天）分为 2 组（n=18）。每组再根据饮用水中 F 的浓度分为 3 个亚组（n=6）：0mg/L（对照）、15mg/L 或 50mg/L。实验结束后，麻醉动物并采集肝脏和血液。测定血浆和肝脏中的 F。部分肝脏固定用于组织学分析。提取肝脏蛋白并进行定量无标记质谱分析。与对照组相比，无论暴露时间如何，50mg/L 组的血浆和肝脏中的 F 浓度均显著升高。在接受 20 天治疗的亚组中，肝脏的组织学改变更为明显。蛋白质组学分析显示，暴露于 F 后，与内质网和线粒体氧化应激、线粒体改变、细胞凋亡和细胞呼吸相关的蛋白质发生变化。这些结果证实了先前的发现，即 F 对肝脏的影响是剂量和时间依赖性的，并为理解这些影响的演变提供了分子基础。
