## 4 Discussion  
As is already well known, oxidative stress is a factor that negatively affects the functioning of the body, thus causing a number of adverse effects. The Nrf signaling pathway is significantly related to oxidative stress as its activation is caused, inter alia, by reactive oxygen species. Under physiological conditions, the transcription factor Nrf2 is bound to the Keep 1 (kelch-like ECH = associated protein 1) protein in the cytoplasm. In the presence of ROS, this complex is degraded, which leads to the translocation of the Nrf2 factor to the cell nucleus, and consequently, causes its attachment to the ARE (antioxidant response element) sequence and the transcription of the genes whose protein products have cytoprotective activity. It has been proven that its activation provides protection against oxidative stress [32]. There are many reports in the latest scientific literature about the involvement of Nrf2 in many disease entities [33; 34]. Nrf2 could play an important role in the prevention of various diseases, as well as during the therapy that is used to treat them. First of all, this applies to cancer as well as other human diseases, including cardiovascular diseases and diabetes as well as neurodegenerative diseases, e.g., Alzheimer's disease, or other disorders of the internal organs. The function of the Keep1-Nrf2 system in monitoring cellular redox imbalance, and thus in the aging process, has also been widely described. Other more complex regulatory networks that are associated with this signaling pathway have been identified as well [35; 36]. [PERSON] et al. [37] proved that Nrf2 protects the cells of the nucleus pulposus against oxidative stress. These reports are identical to the conclusions that were drawn in the course of the presented study in terms of fluoride-induced redox homeostasis disorders and the role of the Nrf2 factor. Figure 3: Correlation between the selected mRNA and miRNA: miR-28-3p vs. _NFE2L2_ (**A**), mir-29-1-5p vs. _NFE2L2_ (**B**) and miR-14-1-3p vs. _KEAP1_ (**C**). This and our previous studies [38; 39] have shown that fluoride disrupts redox homeostasis and disrupts the ability of cells to protect themselves against oxidative stress by reducing the _NFE2L2_ expression. In the NHDF cells that had been treated with NaF, there was an increase in malondialdehydedehyde (MDA) concentration, which is an indicator of lipid peroxidation as well as an increase in the intracellular ROS. At the same time, the presence of fluoride reduced the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) [39]. In turn, the exposure of cells to a static magnetic field restored the redox balance and activated the cells, allowing them to defend themselves against stress, which was manifested by the up-regulation of the _NFE2L2_ expression and also increased activity of the antioxidant enzymes (superoxide dismutase--SOD and glutathione peroxidase--GPx) compared to the cells that had only been treated with fluoride [39]. Superoxide dismutase, catalase and glutathione peroxidase are key enzymes that constitute the first line of antioxidant defense, and their role is to prevent the formation of hydroxyl radicals. Furthermore, the combined exposure of fibroblasts to fluoride and an SMF resulted in a decrease in the production of intracellular ROS and a decrease in the MDA concentration, as was shown in our previous report [39]. Moreover, the RT-qPCR analysis showed statistically significant changes in the expression of the genes such as _SOD1_, _SOD2_ and _GSR_ (glutathione reductase) that belong to the Nrf2 downstream genes. The mRNA level of these genes was lower in the NaF-treated fibroblasts than in the control cells. However, a significant increase in their expression was revealed in the cells that had been co-exposed to fluoride and an SMF with a 0.65 T flux density [23; 38]. A similar trend was followed by [PERSON] et al. [40]. They observed that the level of intracellular ROS increased dramatically after treatment with NaF.