Initial Study of Cognitive Function Impairment as Caused by Chronic Fluorosis.

Abstract

Objective: To investigate whether an impairment in cognitive function exists in parents diagnosed with fluoride poisoning as well as its biological basis.

Methods: Individuals suffering from fluoride poisoning from a high fluorine region were selected for the study group, while healthy individuals from a non-endemic region were selected as the control group. Using specific psychological methods, the indices of blood oxidatative stress were also tested with the following: Thiobarbituric acid reaction (TBA) for Serum lipid peroxide (LPO), Ellman’s for reduced glutathione (GSH) in serum, nitrite method for superoxide dismutase (SOD) in red blood cells, and the Dithiobis-nitrobenzoic acid (DTNB) method for glutathione peroxidase (GSH-Px) in serum. As to determining the amount of NO In the subjects, this was done through testing the nitrous and nitrate (NO2/NO3-) in serum.

Results: Between the study group and the control group, significant differences were observed in the data gathered from the psychological tests. Big differences were found in the tests of language fluency, recognition, similarity, associative learning, and working memory (digit span test). The total failure numbers from the psychological tests and the concentration of NO demonstrated a significant positive correlation, while the similarity test showed a significant negative correlation. SOD activity showed a significant negative correlation with the similarity and digit span tests.

Conclusion: The results suggest that some cognitive function limitations exist in those suffering from chronic fluoride poisoning, and its biologic basis may be related to the levels of SOD and NO.

Keywords: Chronic Fluoride Poisoning; Cognitive Function; Oxidative Stress

EXCERPTS:

1. Subjects and Methods

1.1 Subjects

1.1.1 Study Group. Individuals suffering from fluoride poisoning were selected from an endemic area in Bijie City, Guizhou Province, which is not an area impacted by iodine-deficiency.

Selection criteria. Individuals with fluoride poisoning were identified as those with a diagnosis of dental fluorosis, a decrease in bone density upon X­-ray examination, a thickening of the periosteum, calcification of the skeletal muscle and ligaments, and a decrease in physical fitness and cholinesterase activity, etc. Selection was further limited to subjects between the ages of 30 and 50, who had been suffering from the disease for over 2 years, who had not yet accepted systemic treatment or used antioxidants, who had been excluded from experiencing symptoms of mental disorders caused by stunted mental development and/or organic and somatic diseases of the brain. 49 individuals (37 males, 12 females) were selected in total, all of whom were farmers. The average age was 42±6 years and the average length of education was 10±2 years 20 people from the group obtained a high school degree, 25 completed junior high, and 4 completed their primary studies. The average duration of the disease among these subjects was 32±6 months.

1.1.2 

Control group. The subjects were all healthy residents from the Tongren area of Guizhou Province (an area not impacted by neither iodine-­deficiency nor endemic fluorosis). Selection criteria. Control subjects could not have any bodily and/or mental diseases and their 1st degree relatives could not have any history of neural and/or mental diseases. We selected controls whose gender, age and education level were not statistically different than that of the study group (P<0.05). 39 people were selected and all were farmers; 26 of this group were males and 13 were females. The average age was 43±6, and the average years of completed schooling was 10±3 years. 19 of the controls obtained a high school degree, 18 finished junior high, and 2 completed primary school.

3. Discussion

Among those suffering from chronic fluorosis, research has found that certain injuries occur to bodily functions, with the biological basis for these injuries relevant to the increase in the oxidative stress level of brain tissue caused by long-­term consumption of excess fluorine.[2] In particular, active oxygen produced by oxidative stress and the resulting injury to secondary cells critical role in the development of nerve cells. Under regular conditions, the body has a complete antioxidant defense system. SOD is an important antioxidant enzyme in the body. This study demonstrates that SOD activity has a negative correlation with the body’s executive functions and working memory. This trend towards increased levels of oxidation in the bodies of those suffering from chronic fluorosis indicates that the body’s defense system against free radical agents is impaired. This, in turn, could cause the peroxidation of cell lipids and DNA damage, which could injure certain channels inside the neural cells, leading to the defects of certain cognitive functions found in fluorosis patients.[2] Meanwhile, the compensatory mechanisms in the body, and the compensatory activity of the SOD (which acts as an important antioxidant enzyme) increases, implying that the biological basis of the cognitive deficits among patients with chronic fluorosis is correlated to SOD.

An excessive amount of NO has cytotoxic effects on the nervous system [3]. The effect of NO has brought researchers’ attention on the process by which cell damage results from active oxygenic elements. In this study, we found that the concentration of NO in blood serum presents a negative correlation with the body’s executive functions, which indicates that the cognitive deficits in patients with chronic fluorosis may be related to the level of oxidative stress. With the increased concentration of NO, damage is inflicted on the cell. Certain neuarl channels are particularly impacted by such damage, which can result in  a decline of the cognitive functions executed by these affected neural channels.

In this study, only SOD and NO were found to be related to the cognitive function results among the chronic fluorosis patients, thereby indicating that these two oxidative stress parameters likely had a hand in impairing the patients’ cognitive function. In the process of cell damage induced by oxidative stress, SOD and NO are the two parameters found to be most closely related to the damage [4]. Studies show that SOD has a clear role in the reduction of NO’s poisoning effects on nerves. In the cerebral cortex and neostriatum, NO-­positive neurons have high levels of SOD. This defense mechanism helps to regulate against impairments in the human mechanism anti-oxidant system. This is the reason why cognitive function among those suffering from chronic fluorosis decreases at a relatively static or slow speed, which makes it hard to detect.

References

[1] Ding Guizhi. The Medical Effect of Fluoride on Osteoporosis and Fundamental Treatment [J]. Chinese Journal of  Osteoporosis, 1995, 16(1):38-­43.

[2] Shao Qianli, Wang Yanan, Guan Zhizhong. The Influence of Free Radical Inducer on Brain Oxidation of Fluorosis Rats [J]. Chinese Journal of Preventive Medicine, 2000, 34(6):330-­332.

[3] Dawson VL, Dawson TM, London ED, et al. Nitric oxide mediate glutamate neurotoxicity in primary cortical cultures [J]. Proc Natl Acad Sci USA, 1991, 88(6):6368-­6371.

[4] Lipton SA, Choi YB, Pan ZH, et al. A redox-­based mechanism for neuroprotective and neurodestructive effects of nitric oxide and its compounds [J]. Nature, 1993, 364(10):636-­642.

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Translated from Chinese into English by FoxTranslate, courtesy of the Fluoride Action Network (2012). For more translations of Chinese research on fluoride toxicity, see http://www.fluoridealert.org/researchers/translations/