Vrednotenje endokrinih učinkov in reproduktivne toksičnosti sestavin eteričnega olja sivke in silico

Tavčar, Klara (avtor), Jakopin, Žiga (mentor)

Eterično olje sivke je pogosto uporabljena sestavina v kozmetičnih izdelkih, znana po pomirjujočem, sproščujočem učinku ter prijetnem vonju. Poleg vseh terapevtskih učinkov sivke, zaradi katerih se sivka uporablja tudi v aromaterapiji, na dan prihajajo raziskave in študije, v katerih eterično olje sivke povezujejo z neželenim hormonskim delovanjem. Pri zdravih otrocih in dojenčkih je prišlo do nenavadne ginekomastije, kjer se je le-ta pojavila ob uporabi kozmetičnih izdelkov z eteričnim oljem sivke, ob opustitvi izdelka pa izginila. Gre za stanje, povezano z motnjo signaliziranja steroidnih hormonov pri moških, ki se kaže v povečanem ali nenamernem izločanju estrogena in posledično rasti prsnega tkiva. V diplomski nalogi smo z in silico metodami generirali napovedi endokrinega delovanja in reproduktivne toksičnosti posamičnih sestavin eteričnega olja sivke. Komponente eteričnega olja sivke, ki smo jih analizirali, smo izbrali na podlagi sestave eteričnega olja sivke iz literature. S programoma Endocrine Disruptome in VegaNIC smo predvideli vezavo komponent izbranega eteričnega olja sivke na hormonske jedrne receptorje, s programi T.E.S.T, Derex Nexus in VegaNIC pa smo napovedali reproduktivno toksičnost posameznih komponent. Rezultati napovedi vezave teh komponent na hormonske receptorje nakazujejo na največjo možnost vezave sestavin eteričnega olja sivke na antagonistično konformacijo androgenskega receptorja ter agonistično konformacijo estrogenskega receptorja in so v skladu z literaturnimi podatki, kjer so poročali o šibkem antiandrogenem ter estrogenem delovanju eteričnega olja sivke in vitro. Napovedi reproduktivne toksičnosti pa nismo uspeli podkrepiti z literaturnimi navedbami, saj kljub temu, da so programi za določene spojine napovedali reproduktivno toksičnost, v literaturi nismo naleteli na kakršnokoli povezavo eteričnega olja sivke z reproduktivno toksičnostjo, kar nakazuje na slabšo napovedno moč reproduktivne toksičnosti in silico. Reproduktivna toksičnost namreč velja za kompleksno in zahtevno vejo toksikologije, katere zaenkrat dostopne metode in silico ne morejo primerno obravnavati. Glede na napovedi programov, podkrepljene z literaturnimi podatki, res obstaja možnost za pojav ginekomastije pri otrocih ob uporabi kozmetičnih izdelkov, ki vsebujejo eterično olje sivke. Lipofilnost eteričnega olja in tanjša otroška koža olajšata tudi samo prepustnost eteričnega olja v globlje plasti kože. Potrebne bi bile nadaljnje raziskave ter študije in vitro in in vivo, s pomočjo katerih bi domnevno hipotezo o eteričnem olju sivke kot hormonskem motilcu lahko potrdili ali ovrgli. Ob kritični in strokovno podkrepljeni interpretaciji rezultatov pa lahko napovedi in silico predstavljajo izhodiščno točko za nadaljnje študije.

• Jezik: Slovenski jezik
• Ključne besede: eterično olje sivke, metode in silico, endokrina toksičnost, reproduktivna toksičnost
• Vrsta gradiva: Diplomsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2020
• PID: 20.500.12556/RUL-117257
• Datum objave v RUL: 03.07.2020

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: In silico evaluation of endocrine effects and reproductive toxicity of lavender essential oil ingredients

Izvleček

Lavender essential oil is widely used ingredient in cosmetic products, known for its pleasant smell and its calming effect. Beside its therapeutic effects and the uses of lavender essential oil in aromatherapy, increasing number of papers report on the association of lavender essential oil and endocrine system. A few clinical cases have described an unusual occurrence of gynecomastia in young healthy children, especially in boys. All patients were using care products which contained lavender essential oil at the time, and following the termination thereof, the gynecomastia disappeared. Gynecomastia is a state associated with steroid hormones signal disorder, which manifests with higher secretion of estrogen hormones and, consequently, in breast growth. In the scope of this Bachelor’s thesis, we have evaluated the endocrine and reproductive toxicity of lavender essential oil components using in silico methods. The selection of the examined compounds was based on the essential oil components reported in the literature. Using Endocrine Disruptome and VegaNIC, we predicted the binding of lavender essential oil components on nuclear hormone receptors, while T.E.S.T, Derex Nexus and VegaNIC were used to predict their reproductive toxicity. The generated results of hormone receptor binding probability indicated a high possibility for lavender essential oil components to bind antagonistic conformation of the androgen receptor and the agonistic conformation of the estrogen receptor. The in vitro study reported in the literature revealed weak antiandrogen and estrogen effects of lavender essential oil, thus corroborating our prediction. On the other hand, the positive results of reproductive toxicity predictions are not in agreement with the literature, namely no results linking lavender essential oil to reproductive toxicity have been published to date to support our predictions. This shows us that in silico methods are for now still not efficient and accurate enough for predicting something as complex as reproductive toxicity. According to our endocrine effect predictions, there is a real possibility of developing gynecomastia in children using cosmetic products with lavender essential oil. The lipophilicity of essential oil and thinner child skin facilitate the penetration of lavender essential oil into the skin. Therefore, further in vitro as well as in vivo investigations are needed to determine the effects of lavender essential oil on the endocrine system. Nevertheless, the in silico predictions can serve as a good starting point for further research, if interpreted by a professional.

• Ključne besede: lavender essential oil, in silico methodology, endocrine system, reproductive toxicity