###### Abstract  
Many physical and chemical factors can influence the Nrf signaling pathway, and its deregulation has been associated with various disease states. Nrf2 and Keep1 molecules are key elements that regulate the response under cell stress conditions. Hence, the aim of the research was to assess the impact of a static magnetic field that was generated by permanent magnets on the transcriptional activity of the _NFE2L2_ and _KEAPI_ genes in a human dermal fibroblast cell line that had been cultured with fluoride ions and in an environment without them. Additionally, our research aimed to answer the question of whether the regulatory RNA molecules--miRNAs--are involved in these effects. Experiments were performed on an NHDF cell line that had been treated with fluoride ions, along with simultaneous exposure to a moderate-intensity static magnetic field. The RT-qPCR method was used to determine the mRNA level of the _NFE2L2_ and _KEAPI_ genes and the miRNA level of miR-28-3p, miR-29b-1-5p, miR-141-3p and miR-365a-3p. Our results indicate that fluoride ions influence the Nrf signaling pathway and that miRNAs are involved in regulating it. Moreover, the static magnetic field had a beneficial effect on the cells with fluoride-induced oxidative stress due to stimulating the antioxidant defense. static magnetic field; fluoride; skin fibroblasts; microRNA; Nrf2 transcription factor +
Footnote †: journal: Applied Sciences  
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Footnote †: journal: Applied Sciences  
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oxidoreductase 1 and various cytochrome P450s), phase II (glutathione \(S\)-transferases, UDP-glucuronosyltransferase and heme oxygenase-1) and phase III (drug efflux transporters). Moreover, Nrf regulates the expression of the genes that participate in reducing oxidized protein thiols (thioredoxin, thioredoxin reductase 1, sulfiredoxin). The induction of the Nrf2 signaling cascade has been found to counteract the effects of the disruption of cellular redox homeostasis [8]. The generation of oxidative stress is influenced by many factors, including stress, environmental pollution [9], smoking [10] and overexposure to solar radiation [11]. In addition, factors that increase the production of reactive oxygen species (ROS) also include fluoride compounds, which people are often exposed to during their everyday lives. Despite the documented positive effects of fluoride on the body (including maintaining the proper structure of the skeleton), it should be borne in mind that exposure to fluoride and its compounds in incorrect doses may have negative effects and cause many unfavorable changes in the body [12; 13]. An inadequate intake of fluoride may adversely affect the functioning of many organs, including the kidneys and liver, by, e.g., contributing to an increased risk of developing renal failure or necrotic changes in the liver. Fluoride hyperglycemia has also been reported. The neurotoxicity of fluoride compounds consists of the appearance of neurodegenerative changes in the brain structures and the reduction in the receptors in the brain. In addition, fluoride can lead to changes in the functioning of the reproductive system as well as changes in the mineral status of the body. The harmful effects of this compound depend on the duration of the exposure. The dose and its ability to accumulate in the tissues are also not insignificant [14; 15]. These changes can result from the role of the fluoride compounds in modifying the molecular pathways, including the NRF2/KEAP1 pathway in cells. Histological changes in the myocardium after NaF (sodium fluoride) had been administered, which was the result of an excessive accumulation of reactive oxygen species and was related to the above-mentioned molecular pathway, have also been demonstrated [16]. Moreover, in an animal model, the negative effect of fluoride on lung cells as a result of oxidative stress has also been confirmed.