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Ma, Yan-Lin; Deng, Jie; Zhang, Ting; Li, Hong-Mei; Liang, Qiu-Zhe; Zhang, Kai-Lin
Journal of trace elements in medicine and biology, December 2023, 2023-12-00, 20231201, Letnik: 80Journal Article
This investigation was designed to examine the potential involvement of RAGE/NADPH oxidase signaling in the damage to the brain caused by chronic fluorosis. Sprague-Dawley rats were divided randomly into 9 groups each containing 20 animals, Controls (C); rats receiving low (i.e., 10 ppm) (LF) or high does ( i.e., 50 ppm) (HF) of fluoride in their drinking water; and these same groups injected with FPS-ZM1, an inhibitor of RAGE, (CF, LFF and HFF, respectively) or administered EGb761, an active ingredient of Ginkgo biloba extract, intragastrically (CE, LFE, and HFE). Following 3 and 6 months of such treatment, the spatial learning and memory of the animals were assessed with the Morris water maze test; the levels of malondialdehyde (MDA), hydrogen peroxide (H2O2) and superoxide dismutase (SOD) assayed by biochemical methods; and the levels of proteins related to the RAGE/NADPH pathway determined by Western blot and of the corresponding mRNAs by qPCR. After 6 months, the spatial learning and memory of the LF and HF groups had declined; their brain contents of MDA and H2O2 increased and SOD activity decreased; and the levels of the RAGE, gp91, P47, phospho-P47phox and P22 proteins and corresponding mRNAs in their brains were all elevated. Interestingly, all of these pathological changes caused by fluorosis could be attenuated by both FPS-ZM1 and EGb761. These findings indicate that the brain damage induced by fluorosis may be caused, at least in part, by enhanced RAGE/NADPH oxidase signaling and that FPS-ZM1 or EGb761 might be of clinical value in connection with the treatment of this condition. •Exposure of rats to a high level of fluoride in their drinking water for 6 months impaired their spatial learning and memory and increased the level of oxidative stress in their brains.•Exposure of rats to fluorosis elevated the levels of the RAGE, gp91, P47, phospho-P47phox and P22 proteins and of the corresponding mRNAs in their brains.•Concomitant treatment with FPS-ZM1 or EGb761 alleviated these changes in the brain induced by fluorosis, perhaps by enhancing RAGE/NADPH oxidase signaling.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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