Kaja Ovijač (Avtor), Žiga Jakopin (Mentor)

Povzetek

Zaradi škodljivih učinkov UV sevanja narašča ozaveščenost o uporabi kozmetičnih izdelkih za zaščito pred soncem, ki kot aktivne sestavine vsebujejo UV-filtre. Te lahko najdemo tudi v drugih kozmetičnih izdelkih, zato smo jim pogosto izpostavljeni. Zaradi njihove razširjene uporabe se nahajajo tudi v podtalnici, odpadnih vodah in rekah. Pojavlja se vprašanje ali so te sestavine varne za zdravje ljudi in uporabo na njih. V diplomski nalogi smo z in silico metodami vrednotili endokrino in reprodukcijsko toksičnost izbranih cinamatov in njihovih metabolitov. Dobljene rezultate smo primerjali z že objavljenimi in vitro ter in vivo študijami. Izbrana cinamata sta 2-etilheksil metoksicinamat in izoamil metoksicinamat. Oba sta kot UV-filtra dovoljena tako na evropskem kot tudi ameriškem trgu. V večini se v kozmetičnih izdelkih uporablja 2-etilheksil metoksicinamat, izoamil metoksicinamat pa redkeje. Raziskovanja smo se lotili s pomočjo in silico metodologije, ki bi lahko v prihodnosti nadomestila in vitro ter in vivo raziskave in s tem zmanjšala poizkuse na živalih. Potencialne metabolite izbranih cinamatov in njihove metabolne poti smo napovedali s programom Meteor Nexus. Napovedane metabolite smo uporabili za nadaljnje raziskave. S programom Endocrine Disruptome ter VEGA (Estrogen Receptor Relative Binding Affinity model) smo napovedali vezavno afiniteto cinamatov in njunih metabolitov na 12 različnih jedrnih receptorjev. S programom Derek Nexus, VEGA (Developmental Toxicity model) in TEST pa smo napovedali različne vidike reprodukcijske toksičnosti izbranih cinamatov in njunih metabolitov. Pri napovedi s programom Meteor Nexus so se napovedi za nekatere metabolite dobro ujemale z literaturnimi podatki. Večine napovedanih metabolitov v literaturi nismo zasledili, zasledili pa smo metabolite, ki jih program ni napovedal. Pri preučevanju endokrinih učinkov je program napovedal srednjo verjetnost vezave enega ali obeh cinamatov in vseh ali samo nekaterih metabolitov na tiroidni receptor, androgenski receptor v antagonistični konformaciji in glukokortikoidni receptor. Za estrogenski receptor je napovedal neaktivnost. Rezultati o napovedi reprodukcijske in razvojne toksičnosti so bili za oba cinamata neenotni, enotni pa le za metabolit 2-EH, kar potrjujejo tudi obstoječe študije. In silico metode so se izkazale za uporabne v začetnih fazah raziskovanja ali pa nam pomagajo pri obdelavi velike količine podatkov. V tem trenutku pa se na njih še ne moremo zanesti v takšni meri, da bi z njimi nadomestili in vivo in in vitro raziskave. V prihodnosti bo potrebna njihova nadgradnja in strokovna presoja o dobljenih rezultatih.

Ključne besede

cinamati;in silico metode;endokrina toksičnost;reproduktivna toksičnost;

Podatki

Jezik: Slovenski jezik
Leto izida:
Tipologija: 2.11 - Diplomsko delo
Organizacija: UL FFA - Fakulteta za farmacijo
Založnik: [K. Ovijač]
UDK: 612.015.3+615.9(043.2)
COBISS: 4638065 Povezava se bo odprla v novem oknu
Št. ogledov: 628
Št. prenosov: 143
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Angleški jezik
Sekundarni naslov: In silico evaluation of metabolism, endocrine effects and reproductive toxicity of selected cinnamates
Sekundarni povzetek: People are becoming more and more aware of the harmful effects of UV radiation, which results in increased use of cosmetic products for sun protection that contain UV filters as active ingredients. These can also be found in other cosmetic products, which is why we are often exposed to them. As they are so widely used, they can also be found in groundwater, waste water and rivers. The question is whether these ingredients are safe for people or they pose a threat to human health. This thesis evaluates the endocrine and reproductive toxicity of chosen cinnamates and their metabolites through in silico methods. The results are then compared with already published in vitro and in vivo studies. The chosen cinnamates are 2-ethylhexyl methoxycinnamate and isoamyl methoxycinnamate. Both are allowed as UV filters on the European as well as the American market. Most cosmetic products contain 2-ethylhexyl methoxycinnamate while the isoamyl methoxycinnamate is used less often. The research was done with the use of in silico methods which could in the future replace in viro and in vivo research and reduce animal testing. The potential metabolites of the chosen cinnamates and their metabolic pathways were predicted with the Meteor Nexus program. The predicted metabolites were used for additional research. With the Endocrine Disruptome program and VEGA (Estrogen Receptor Relative Binding Affinity model) we have predicted the binding affinity of cinnamates and their metabolites to 12 different nuclear receptors. With the use of the Derek Nexus program, VEGA (Developmental Toxicity model) and TEST we have predicted the different aspects of the reproductive toxicity of the chosen cinnamates and their metabolites. Predictions made with the Meteor Nexus program matched the data in literature for some of the metabolites. Most of the predicted metabolites however, could not be found in literature while we have found certain metabolites in literature that the program did not predict. While studying the endocrine effects, the program predicted medium level of likelihood of binding one or both cinnamates and all or some metabolites to the thyroid receptor, androgen receptor in the antagonist conformation and glucocorticoid receptor. The software predicted inactivity for the estrogen receptor. The results of the prediciton for reproductive and developmental toxicity were inconclusive for both cinnamates and conclusive only for the 2-EH metabolite, which has also been confirmed by the existing studies. In silico methods have proven themselves useful in early stages of research or while processing large quantities of data. However, at this time they are not reliable enough to be able to replace in vivo and in vitro research. In the future they will require further upgrades and expert evaluation of the obtained results.
Sekundarne ključne besede: Metabolizem;Toksičnost;
Vrsta dela (COBISS): Diplomsko delo/naloga
Komentar na gradivo: Univ. v Ljubljani, Fak. za farmacijo, študij kozmetologije
Strani: 70 f.
ID: 10989830