The aim of the work was to investigate the effect of aluminum chloride or iron dextran in the presence of inhalation anesthetics (IA, sevoflurane and isoflurane) on the accumulation of metals in brain cells, disruption of essential elements and their role in changing redox homeostasis, inflammation, activation of macrophages and glial cells, hepcidin level, ferritin and metalloproteinase activities and the resulting structural and functional changes that lead to the development of neurodegenerative diseases. The results indicate that subacute and especially chronic use of IA with excessive metal intake disrupts cellular metabolism, leads to disruption of essential and accumulation of highly toxic and non-essential metals, increased OS, inflammation, macrophage polarization, immune suppression and minor histopathological changes in the brain through amyloid accumulation. Isoflurane in combination with metals causes the greatest changes in the brain through the extreme accumulation of highly toxic metals. The data indicate a link between high hepcidin levels, inflammation, polarization of macrophages towards the M1 phenotype, increased AChE, decreased BDNF and neurodegenerative damage. The level of hepcidin is closely related to macrophage polarization, OS, inflammation and reorganization of damaged tissue, while ferritin and arginine and anti- inflammatory cytokines and BDNF are protective components of the brain in the presence of metals and/or IA. Furthermore, microenvironmental conditions affect macrophage plasticity and the relationship between M1/M2 macrophage phenotypes; iron regulates the function of macrophages through multiple pathways, affecting their polarization, enzymatic activity and overall role in inflammation and immune response. During chronic administration, metals suppress the immune response through a mechanism related to oxidative stress.