@misc{Maciejewska_Alicja_Assessment_2024,
 author={Maciejewska, Alicja},
 address={Kraków},
 howpublished={online},
 year={2024},
 school={Rada Dyscypliny Nauki farmaceutyczne},
 language={pol},
 abstract={Human exposure to the harmful effects of ultraviolet radiation requires the use of appropriate sun protection, mainly in the form of cosmetic products containing UV filters. Unfortunately, in addition to their protective effect, some of these compounds are absorbed through the skin and consequently have systemic side effects. The subject of the research presented in this dissertation is one of the most widely used chemical filters around the world – 2-hydroxy-4-methoxybenzophenone, called benzophenone-3 or oxybenzone, which, due to its photoprotective properties, is used in many industries, including sunscreen products. Although benzophenone-3 has been proven to disrupt the functions of the endocrine system, it is still widespread, which is reflected in the high degree of human exposure to this substance, as research indicates that it may affect almost the entire society. Benzophenone-3 is a lipophilic compound, as a result of which it may accumulate in adipose tissue and internal organs. Studies conducted on rats have shown that benzophenone-3 crosses the blood-brain barrier, and this compound has also been detected in the white matter tissue of the human brain in postmortem studies. Unfortunately, not only adults are exposed to the harmful effects of benzophenone-3. The presence of benzophenone-3 was found in placental tissue, amniotic fluid, umbilical or fetal blood, and in},
 abstract={mother's milk, which indicates that exposure to benzophenone-3 may occur already in the prenatal and neonatal period, i.e. in periods when cells, especially nerve cells, are the most sensitive to damage. Research indicates that prenatal exposure to benzophonone-3 may be associated with an increased risk of Hirschprung's disease in newborns, manifested by a deficit of intestinal innervation. Previous in vitro and in vivo studies on the effect of benzophenone-3 on the central nervous system indicate that this compound may have a neurotoxic effect on nerve cells, induce apoptosis, as well as disturb intracellular signal transduction pathways. However, the exact mechanisms of action of benzophenone-3 have not been known, in particular there are no studies determining the effect of this compound on immunoactivation in the central nervous system. One of the important mechanisms of the neurotoxic effect of xenobiotics is the activation and polarization of microglia cells, which, by secreting pro-inflammatory cytokines, damage nerve cells, consequently leading to impairment of their functions or death. Taking into account that the influence of benzophenone-3 on the functions of microglial cells and the importance of their activation in nerve cell damage has not been assessed so far, the aim of my doctoral thesis was to determine in in vivo and in vitro studies whether this compound has},
 abstract={the ability to activate microglial cells leading to their polarization in the pro- or anti-inflammatory direction. The main aim of the in vivo studies was to evaluate selected M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia markers and transcription factors regulating their activation after prenatal and adult exposure to benzophenone-3 in male Sprague-Dawley rats. Moreover, the aim of the study was to assess markers of oxidative stress in the brain structures most sensitive to damage, i.e. the hippocampus and frontal cortex, as well as to check whether benzophenone-3 can induce types of cell death other than apoptosis. In turn, in vitro studies conducted in primary cultures of microglial cells isolated from rat pups were aimed at determining the phenotypic and functional characteristics (profile of released cytokines) of microglia after exposure to benzophenone-3, as well as assessing the impact of the tested compound on the viability of these cells. Moreover, the aim of the in vitro studies was to determine whether prior incubation of cells with benzophenone-3 could sensitize microglial cells, leading to their subsequent increased activation after stimulation with lipopolysaccharide. The conducted research showed for the first time that exposure to benzophenone-3 leads to the activation and polarization of microglia. Both in vivo and in vitro studies showed a signi},
 abstract={ficant reduction in the expression of the M2 phenotype marker of anti-inflammatory microglia, which may indicate that benzophenone-3 weakens the protective effect of microglia and, as a result, promotes the polarization of microglia towards M1 microglia with pro-inflammatory activity. The polarization of microglia towards the M1 phenotype observed in the frontal cortex was accompanied by an increase in the level of NF-κB - the main transcription factor responsible for activation of the immune system, and an increased level of the active form of caspase-1, an enzyme that activates pro-inflammatory cytokines. In the hippocampus, despite a reduction in the level of the M2 microglia phenotype marker, we did not find any changes in the level of NF-κB and caspase-1, nor an increased CD86/CD206 protein ratio, which may result from an increased level of the glucocorticoid receptor, a transcription factor that inhibits immunoactivation, mainly through the interaction with the NF-κB factor in this structure. The differences demonstrated between the examined brain structures are consistent with previous results indicating that benzophenone-3 induces apoptosis mainly in the frontal cortex and not in the hippocampus. Also in vitro (in primary culture of microglial cells), both by fluorescence staining and flow cytometry, benzophenone-3 was shown to promote microglial polarization towards pr},
 abstract={o-inflammatory M1 microglia. Importantly, benzophenone-3 also showed the ability to enhance lipopolysaccharideinduced changes in both the phenotype of microglial cells and pro-inflammatory cytokines, such as IL-1α, IL-1β or TNFα released by these cells. The obtained research results provide important data on the adverse effects of benzophenone- 3 on the central nervous system, and also present possible connections between the influence of the benzophenone-3 on microglial cells and the induction of oxidative stress and the increase in extracellular glutamate concentration by this compound. Considering the wide spread of benzophenone-3 in industry and its significant environmental pollution, human exposure to this compound and its potential side effects are still a topical topic. Our research demonstrated that exposure to benzophenone-3 leads to the activation of microglia, which predisposes to the development of inflammation in the central nervous system and may play an important role in the development of neurodegenerative diseases.},
 title={Assessment of microglial cell activation as a result of exposure to benzophenone-3 : in vivo and in vitro studies},
 type={Praca doktorska},
 keywords={benzophenone-3, microglia activation, microglia polarization, cytokines, primary microglia cells, oxidative stress, central nervous system},
}