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Sistematični pregled in primerjava izidov raziskav imunskih učinkov bisfenola A in njegovih nadomestkov
ID Jarc, Manja (Author), ID Sollner Dolenc, Marija (Mentor) More about this mentor... This link opens in a new window

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Abstract
Bisfenol A (BPA) je organska sintetična spojina, ki spada v skupino motilcev endokrinega sistema. Najdemo jo v številnih plastičnih izdelkih, kot so embalaže za živila, pločevinke, zobna tesnila, otroške igrače, posode za pijačo in termični papir. Predvsem z vezavo na različne hormonske in ostale receptorje vpliva na delovanje endokrinega, imunskega in srčno-žilnega sistema. V nekaterih izdelkih so BPA zamenjali njegovi nadomestki, ki pa imajo večinoma podobno kemijsko strukturo, fizikalno-kemijske lastnosti in posledično tudi delovanje ter toksične učinke. Namen te magistrske naloge je bil pripraviti pregled učinkov BPA in njegovih nadomestkov na imunski sistem in jih primerjati. Podatke za sistematični pregled literature smo črpali iz dveh podatkovnih baz PubMed in ScienceDirect. Za selekcijo člankov smo uporabili metodologijo PRISMA in izbrali relevantne raziskave, ki so se navezovale na našo tematiko in raziskovalno vprašanje. Ugotovili smo, da je bilo o vplivu na imunski sistem največ raziskav narejenih za BPA in njegove analoge bisfenol S (BPS), bisfenol F (BPF) in bisfenol AF (BPAF), zato smo rezultate njihovih raziskav primerjali med seboj. BPA in analogi so pokazali največji vpliv na mononuklearne celice človeške periferne krvi (PBMC), kamor spadajo limfociti T, limfociti B, monociti, naravne celice ubijalke in dendritične celice. S povečanjem nastanka reaktivnih kisikovih zvrsti, hidroksilnih radikalov in lipidne peroksidacije sta se zmanjšala proliferacija in preživetje celic. Bisfenoli so prek različnih signalnih poti in transkripcijskih faktorjev vplivali na razmerje provnetnih in protivnetnih citokinov ter v večini primerov pospeševali nastanek vnetja v telesu. V zadnjem delu magistrske naloge smo se osredotočili na kritične imunotoksikološke učinke BPA, zaradi katerih je znanstveni odbor Evropske agencije za varnost hrane (EFSA) znižal začasni dopustni vnos (TDI) za BPA s 4 µg/kg/dan na trenutno veljavni TDI 0,2 ng/kg/dan. Pri raziskovanju smo ugotovili povezavo med izpostavljenostjo BPA v nosečnosti ali zgodnjem otroštvu in razvojem alergijske astme s piskajočim dihanjem. Ugotovljena kritična učinka sta bila tudi povečanje števila specifičnih IgE pri alergijskem vnetju pljuč in povečanje števila celic Th17. Največji zaviralni učinek na imunski sistem smo ugotovili pri nadomestkoma BPF in BPAF, medtem ko BPS deluje bolj kot aktivator imunskega sistema ter povzroča preobčutljivostne in alergijske reakcije. V prihodnosti lahko pričakujemo vedno več alternativ BPA, ki bodo zamenjale uporabo bisfenolov v izdelkih. Tak primer je Pergafast 201, ki se sicer že uporablja v proizvodnji termičnega papirja, vendar potrebujemo še veliko raziskav o njegovi toksičnosti ter varni uporabi v vsakdanjem življenju.

Language:Slovenian
Keywords:bisfenol A, analogi BPA, alternative BPA, prirojeni imunski sistem, pridobljeni imunski sistem
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2023
PID:20.500.12556/RUL-149260 This link opens in a new window
Publication date in RUL:06.09.2023
Views:461
Downloads:44
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Secondary language

Language:English
Title:Systematic review and comparison of research outcomes on the immune effects of bisphenol A and its substitutes
Abstract:
Bisphenol A or BPA is an organic synthetic compound that belongs to the group of endocrine disruptors. It can be found in many plastic products such as food packaging, cans, dental sealants, children's toys, beverage containers and thermal paper. BPA can affect the endocrine, immune and cardiovascular systems by binding to various hormone and other receptors. In some products, it has been replaced by its substitutes, which have a similar chemical structure, physico-chemical properties, mechanisms and toxic effects. The aim of this master's thesis was to review and compare the effects of BPA and its substitutes on the immune system. The data for the systematic literature review were extracted from two databases: PubMed and ScienceDirect. We used the PRISMA methodology to select articles and studies that were relevant to our topic and research question. We found that most studies of the impact on the immune system were done for BPA and its analogues bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF), and therefore compared the results of their studies with each other. BPA and analogues had the greatest impact on human peripheral blood mononuclear cells (PBMC), which include T lymphocytes, B lymphocytes, monocytes, natural killer cells and dendritic cells. Increases in reactive oxygen species, hydroxyl radicals and lipid peroxidation have been associated with decreased cell proliferation and survival. Bisphenols influenced the ratio of pro-inflammatory to anti-inflammatory cytokines through various signalling pathways and transcription factors, in most cases promoting the development of inflammation in the body and slowing down the arrival of immune cells at the site of inflammation. In the last part of the master's thesis, we focused on the critical immunotoxicological effects of BPA, which led the EFSA's CEP Panel to lower the provisional TDI for BPA from 4 µg/kg/day to the currently valid TDI of 0.2 ng/kg/day. In our research, we found an association between exposure to BPA during pregnancy or early childhood and the development of allergic asthma with wheezing. Critical effects identified were also an increase in the number of specific IgE in allergic lung inflammation and an increase in the number of Th17 cells. The greatest inhibitory effect on the immune system was found with the substitutes BPF and BPAF, while BPS acts more as an activator of the immune system and causes hypersensitivity and allergic reactions. In the future, various new BPA alternatives are likely to replace the use of bisphenols in products. One such alternative is Pergafast 201, which is already used in the production of thermal paper, but more research on its toxicity and safe use in everyday life is needed.

Keywords:bisphenol A, BPA analogues, BPA alternatives, innate immune system, adaptive immune system

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