Molecular and immunohistochemical alterations in fluoride-induced neurological impediment in adult rats

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2024-08-23 DOI:10.1016/j.jtemb.2024.127511

Sachindra Kumar , Ravindra Shantakumar Swamy , Rashmi Bhushan , Vishal Chhabra , Smita Shenoy , Krishna Murti , Shubhankar Kumar Singh , Nitesh Kumar

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引用次数: 0

Abstract

Summary

This study highlights the potential neurotoxic and impaired behavioral effects associated with high fluoride concentrations in drinking water.

Purpose

Fluoride is known to cause neurotoxicity, evinced by lower I.Q. levels in children from high-fluoride regions as compared to those in low-fluoride regions. Thus, the present study was designed to investigate the molecular mechanism behind the neurological and behavioural changes induced by sodium fluoride in Wistar rats.

Material and methods

A total of 24 female Wistar rats, aged six weeks and weighing approximately 150–220 g, were randomly divided into three groups: Group I (control) received reverse osmosis (R.O.) water, Group II received Sodium Fluoride (NaF) at 10 ppm, and Group III received NaF at 50 ppm in their drinking water for 60 days. The animals underwent behavioural tests including the Forced Swim Test (F.S.T.), Open Field Test (OFT), and Novel Object Recognition Test (N.O.R.T.), to assess any alterations in behaviour. After 60 days, the animals were euthanized, and their blood and brain samples were analysed to evaluate biochemical changes by Western Blot/I.H.C. analysis of B.A.X., Bcl2, LC3B, TLR4, PARP1, p53, Caspase, α-Synuclein, PARKIN, NeuN, KI67, DNM-1, and M.F.N. for assessing molecular pathways for toxicity.

Results

Impaired locomotion, memory impairment, and behaviour resembling depression in the animals were evinced by reduced mobility index in the F.S.T., discrimination index in the N.O.R.T., and reduced locomotor activity in the open field test results. Additionally, alterations in antioxidant levels and oxidative stress parameters were observed in the brain. The expression levels of various apoptotic and inflammatory biomarkers (B.A.X., Bcl2, TLR4, PARP1, p53, and Caspase) showed apoptosis in neurons. The confocal studies showed increased expression of inflammatory (α-Synuclein, PARKIN), apoptotic (LC3B, B.A.X., p53, KI67), and mitochondrial dysfunction (NeuN, DNM-1, M.F.N.) markers in fluoride-treated animals. Toxicity was more prominent in 50 ppm of fluoride-treated animals.

Conclusion

Fluoride showed potent neuronal toxicity as evidenced by alterations of various molecular markers.

查看原文本刊更多论文

氟化物诱发成年大鼠神经功能障碍的分子和免疫组织化学变化

摘要本研究强调了与饮用水中高浓度氟有关的潜在神经毒性和行为损害效应。目的众所周知，氟会导致神经毒性，高氟地区儿童的智商水平低于低氟地区儿童就证明了这一点。因此，本研究旨在探讨氟化钠诱导 Wistar 大鼠神经和行为变化背后的分子机制：第一组（对照组）饮用反渗透（R.O.）水，第二组饮用百万分之 10 的氟化钠（NaF），第三组饮用百万分之 50 的 NaF，连续 60 天。对动物进行行为测试，包括强迫游泳测试（F.S.T.）、开放场地测试（OFT）和新物体识别测试（N.O.R.T.），以评估动物行为的任何改变。60 天后，对动物实施安乐术，分析其血液和大脑样本，通过 Western Blot/I.H.C. 分析 B.A.X、结果动物的运动能力受损、记忆力减退、行为类似抑郁症，表现为F.S.T.移动指数降低、N.O.R.T.辨别指数降低、野外测试结果中运动能力降低。此外，还观察到大脑中抗氧化剂水平和氧化应激参数的改变。各种凋亡和炎症生物标志物（B.A.X.、Bcl2、TLR4、PARP1、p53 和 Caspase）的表达水平显示神经元出现凋亡。共聚焦研究显示，氟处理动物的炎症（α-突触核蛋白、PARKIN）、凋亡（LC3B、B.A.X.、p53、KI67）和线粒体功能障碍（NeuN、DNM-1、M.F.N.）标志物的表达量增加。结论氟化物对神经元的毒性很强，各种分子标记物的改变证明了这一点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.