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      Pathological changes and effect on the learning and memory ability in rats exposed to fluoride and aluminum

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          Abstract

          The aim of this study is to establish a single and combined intoxication model of fluoride and aluminum so as to observe the impact of these chemicals on the learning and memory ability and the pathologic changes in the brains of rats.

          Abstract

          Background: The aim of this study is to establish a single and combined intoxication model of fluoride and aluminum so as to observe the impact of these chemicals on the learning and memory ability and the pathologic changes in the brains of rats. Methods: Forty male Wistar rats were randomly assigned into control (distilled water), fluoride (50 mg L −1 F ), aluminum (100 mg L −1 Al 3+) and combined groups (50 mg L −1 F and 100 mg L −1 Al 3+). The experiment lasted for 3 months. The short-term memory ability and learning and memory ability of the rats were assessed using Y maze and Morris water maze, respectively. At the same time, the concentrations of fluoride and aluminum in urine and brain were measured. The pathologic and microstructural changes in the hippocampus were observed via optical microscopy and transmission electron microscopy, and the expression of the Aβ 1–42 protein was detected using immunohistochemistry. Results: The results showed that the learning and memory ability of each toxicant-exposed group was decreased; the most severe was in the aluminum group, followed by the combined group, and the lightest was in the fluoride group. Although there was no significant difference between all the groups, both fluoride and aluminum could lower the short-term memory ability of the rats. In addition, different pathologic and microstructural changes were observed in fluoride, aluminum and combined groups. Compared with the control group, the expression of Aβ 1–42 protein in the aluminum group was highest, followed by the combined group, and that in the fluoride group was lowest. Conclusions: In conclusion, combined intake of fluoride and aluminum may alleviate the deficits to learning and memory ability caused by aluminum intoxication.

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          Most cited references11

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          Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task.

          This study examined the effect of hippocampal lesions on acquisition of the Morris water maze and conditioned-fear task in inbred mice. C57BL/6J, DBA/2J, and B6D2F1 hybrid mice were given hippocampal lesions or sham surgery and then tested. The lesioned C57BL/6J and B6D2F1 mice failed to learn the Morris task relative to sham-operated controls, and no DBA group learned the task. In the contextual component of conditioned fear, lesions decreased freezing in all strains. But the lesions only affected freezing to the conditioned stimulus in the DBA/2J and B6D2F1 strains. These data demonstrate that C57BL/6J and B6D2F1 mice use the hippocampus to solve the Morris water maze and conditioned-fear task, and the DBA mice use the hippocampus, to some degree, in the conditioned-fear task.
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            Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children.

            Although a dose-effect relationship between water fluoride levels and damage to liver and kidney functions in animals has been reported, it was not demonstrated in humans. To evaluate the effects of drinking water fluoride levels on the liver and kidney functions in children with and without dental fluorosis, we identified 210 children who were divided into seven groups with 30 each based on different drinking water fluoride levels in the same residential area. We found that the fluoride levels in serum and urine of these children increased as the levels of drinking water fluoride increased. There were no significant differences in the levels of total protein (TP), albumin (ALB), aspartate transamine (AST), and alanine transamine (ALT) in serum among these groups. However, the activities of serum lactic dehydrogenase (LDH), urine N-acetyl-beta-glucosaminidase (NAG), and urine gamma-glutamyl transpeptidase (gamma-GT) in children with dental fluorosis and having water fluoride of 2.15-2.96 mg/L and in children having water fluoride of 3.15-5.69 mg/L regardless of dental fluorosis were significantly higher than children exposed to water fluoride of 0.61-0.87 mg/L in a dose-response manner. In contrast to children with dental fluorosis and having water fluoride of 2.15-2.96 and 3.10-5.69 mg/L, serum LDH activity of children without dental fluorosis but exposed to the same levels of water fluoride as those with dental fluorosis were also markedly lower, but the activities of NAG and gamma-GT in their urine were not. Therefore, our results suggest that drinking water fluoride levels over 2.0mg/L can cause damage to liver and kidney functions in children and that the dental fluorosis was independent of damage to the liver but not the kidney. Further studies on the mechanisms and significance underlying damage to the liver without dental fluorosis in the exposed children are warranted.
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              Cilostazol prevents amyloid β peptide(25-35)-induced memory impairment and oxidative stress in mice.

              Cilostazol may be effective in dementia associated with a cerebral ischaemia. In this study, we examined whether it exerts beneficial effects on learning and/or memory impairment induced by Aβ(25-35) in mice, and compared its effects with those of aspirin. Aβ(25-35) (9 nmol) was administered to mice i.c.v. Learning and memory behaviour were evaluated by measuring spontaneous alternation in a Y-maze and a step-down type passive avoidance test, on the 5th and 8th days after injection respectively. Levels of lipid peroxidation (malondialdehyde) and cytokines in the frontal cortex and hippocampus were measured 2, 3, 5 and 7 days after the Aβ(25-35) injection. The effects of repeated administration of cilostazol and aspirin (both at 30 and 100 mg·kg(-1), p.o.) on any changes induced by Aβ(25-35) were evaluated. Repeated administration of cilostazol significantly attenuated the impairment of spontaneous alternation and the shortened step-down latency induced by Aβ(25-35) . Aspirin did not show any beneficial effect. A significant increase in the levels of malondialdehyde (MDA) and IL-1β (only measured in hippocampus) was observed 2, 3 and 5 days after the Aβ(25-35) injection in the frontal cortex and hippocampus. Repeated administration of cilostazol (100 mg·kg(-1)) completely prevented the increase in MDA levels but failed to antagonize the increase in the expression of IL-1β induced by Aβ(25-35). These results suggest that the protective effect of cilostazol on Aβ(25-35)-induced memory impairment may be related to oxidative stress in the frontal cortex and the hippocampus. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.
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                Author and article information

                Journal
                TROEE8
                Toxicology Research
                Toxicol. Res.
                Royal Society of Chemistry (RSC)
                2045-452X
                2045-4538
                2015
                2015
                : 4
                : 5
                : 1366-1373
                Affiliations
                [1 ]Center for Endemic Disease Control
                [2 ]Chinese Center for Disease Control and Prevention
                [3 ]Harbin Medical University
                [4 ]Harbin 150081
                [5 ]China
                Article
                10.1039/C5TX00050E
                375af9f5-ba48-4027-88ad-0f1c4b16f4c6
                © 2015
                History

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