Hialuronskābes/polilizīna hidrogēlu citotoksicitātes mehānismi

Abstract

Darba literatūras apskatā apraksīti hidrogēli, to īpašības un padziļināt apskatīti hialuronskābes un polilizīna hidrogēli. Apkopota informācija par dažādiem šūnu nāves ceļiem kā nekroze, apoptoze, nekropoptoze, piroptoze un feroptoze, padziļināti analizējot feroptozi. Aprakstīta GSH antioksidantu sistēma, glutamīna un cistīna vielmaiņas ceļi, tajos iesaistītie proteīnu un kā izmaiņas tajos ietekmē feroptozi. Kā arī aprakstīti lipīdi, to oksidācija, konkrēti PC un noteikšanas metodes. Veidojot literatūras aprakstu, izmantoti avoti laika posmā no 2000. līdz 2023. gadam, kuri atrasti izmantojot ScienceDirect, SCOPUS, Elsavier datu bāzes. Maģistra darba eksperimentālā daļā iegūti hialuronskābi un polilzīnu saturoši hidrogēli, kas izmantoti, lai analizētu to citotoksicitātes mehānismus. Veikti šūnu eksperimenti, kuros noteikts glutationa daudzums, veikta izotopu marķēta glutamīna izsekošona, lipīdu oksidācijas analīze izmantojot masspektrometru, analizēta glutamīna un cistīna transporta proteīnu ekspresija kā arī veikts šūnu nāves novēršanas mēģinājums pievienojot aktīvos savienojumus. Iegūtie rezultāi ļauj secināt, ka šūnām pēc saskarsmes ar hidrogēliem notiek izmaiņas cistīna glutamīna vielmaiņas ceļos un tiek ietekmēta GSH antioksidantu sistēmas darbība. Var secināt, ka šūnas mirst caur ferooptozes ceļu. Darba apjoms 46 lpp. Darbs satur 17 attēlus, 1 tabulu, izmantoti 46 literatūras avoti.

Hydrogels, their properties, and hyaluronic acid and polylysine hydrogels are discussed in depth in the literature review. Information on various cell death pathways such as necrosis, apoptosis, necropoptosis, pyroptosis and ferroptosis is collected, with an in-depth analysis of ferroptosis. GSH antioxidant system, glutamine and cystine metabolic pathways, proteins involved in them and how changes in them affect ferroptosis are described. Lipids, their oxidation, specific PCs and detection methods are also described. When creating the literature description, sources were used in the period from 2000 to 2023, which were found using ScienceDirect, SCOPUS, Elsavier databases. In the experimental part of the master's thesis, hydrogels containing hyaluronic acid and polylysine were obtained, which were used to analyze their cytotoxicity mechanisms. Cell experiments were carried out, in which the amount of glutathione was determined, isotope-labeled glutamine was traced, lipid oxidation was analyzed using a mass spectrometer, the expression of glutamine and cystine transport proteins was analyzed, and an attempt was made to prevent cell death by adding active compounds. The obtained results allow us to conclude that the cells after contact with hydrogels undergo changes in the metabolic pathways of cystine glutamine and the activity of the GSH antioxidant system is affected. It can be concluded that the cells die through the ferroptosis pathway. Volume of thesis is 46 pages. Thesis contains 17 pictures, 1 table, 46 literary sources are used.