20.500.12556/RUL-134343 Vrednotenje metabolizma in permeabilnosti parabenov v izbranih celičnih linijah in vitro Metabolism and permeability evaluation of parabens in selected cell lines in vitro Parabeni so konzervansi, ki se uporabljajo v kozmetičnih, prehranskih in farmacevtskih izdelkih. Kemijsko so alkil estri para-hidroksibenzojske kisline. Poznamo več vrst parabenov pod različnimi imeni, kot taki se naprimer najpogosteje uporabljajo metilparaben (E218), etilparaben (E214), propilparaben (E216) itn. Zanimali so nas kratkoverižni parabeni, saj imajo ti večjo sposobnost penetracije skozi kožo kot dolgoverižni. Ker sta običajni poti vnosa parabenov v organizem skozi prebavila in skozi kožo, smo za raziskovanje vstopa parabenov izbrali celične linije Caco-2, HepG2 in NCTC2544. Glavna presnovna pot, ki omejuje biološko uporabnost parabenov, je metabolizem do para-hidroksibenzojske kisline. Zato smo v vseh celičnih linijah preverili zmožnost zaznavanja in kvantitativne opredelitve te pretvorbe. S Caco-2 celicami smo določili tudi permeabilnostne lastnosti parabenov in para-hidroksibenzojske kisline. Za sočasno detekcijo različnih spojin v vzorcih smo uporabili HPLC (tekočinska kromatografija visoke ločljivosti) sistem in razvili metodo, ki je dovolj selektivna in občutljiva. Primerna je morala biti za sočasno določanje vseh načrtovanih preiskovanih spojin v dovolj kratkem času, da je omogočala analizo velikega števila vzorcev pridobljenega v poskusih. Opazovali smo kako temeljito se parabeni metabolizirajo in opazili velik del pretvorbe preiskovanih spojin v metabolit že medtem, ko so parabeni prehajali sluznico. Parabens are perservatives used in cosmetics, food and pharmaceuticals. Chemically they are alkyl esters of hydroxybenzoic acid. There are several different types of parabens, under different names, in our thesis we have chosen methylparaben (E218), ethylparaben (E214) and propylparaben (E216). We were interested in short-chain parabens, due to their higher ability to penetrate the skin compared to long-chain parabens. Most important pathways for parabens into organism are through the dygestive system and skin. Therefore we selected Caco-2, HepG2 and NCTC2544 cell lines to measure metabolism and permeability. An HPLC (High Performance Liquid Chromatography) system was used for simultaneous detection of different compounds in samples. A sufficiently selective and sensitive metod was developed for this purpose. The main metabolic pathway, restricting biological use of parabens, is the metabolism to para-hydroxybenzoic acid. Therefore, the ability to detect and quantify this conversion was tested in all cell lines. With theuse of Caco-2 cells the permeability properties of parabens and para-hydroxybenzoic acid were determined. In this thesis, we observed how parabens are being transformed into metabolite, which is para-hydroxybenzoic acid, and came to conclusion that they are quick to enter membrane but as soon as they come into contact with membrane big flux of metabolite was noticed. metabolizem permeabilnost parabeni celične linije metabolism permeability parabens cell lines true false false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2022-01-08 07:45:02 2022-01-08 07:45:15 2022-09-13 03:54:37 0000-00-00 00:00:00 2022 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 86754 6284.pdf 6284.pdf 1 DEE6956D81135901D1EF3E8E95A89324 9b97f5ca282c2aa4d0f13389e1a64410c8e1b16f6ddeb42f20b3cdaf140644ff 5de44981-704e-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152741 Fakulteta za farmacijo 0 0 0