Učinak cisplatine i nanokristala resveratrola na aktivnost inducibilne dušik-oksid- sintaze i hipoksijom induciranog čimbenika 1 u miša nositelja Ehrlichovog solidnog tumora

master's thesis

• Title (english): The effect of cisplatin and resveratrol nanocrystals on the activity of inducible nitric oxide synthase and hypoxia-inducible factor 1 in mice bearing Ehrlich's solid tumor
• Author: Ivana Turk
• Mentor: Snježana Ramić (mentor)
• Mentor: Nada Oršolić (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-12-05, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Cilj ovog istraživanja bio je istražiti združeno djelovanje otopine resveratrola i njegovih nanokristala u dozi od 50 mg/kg primjenjeni peroralno (po) i cisplatine injicirane intraperitonealno (ip) u dozi od 2,5 mg/kg, 10. i 12. dan te 15. dan u dozi od 5 mg/kg, na rast solidnog oblika Ehrlichovog ascitesnog tumora (sEAT). Miševima soja Balb/C je u područje desnog bedra supkutano inokulirana suspenzija stanica EAT koncentracije 1x106. Životinje su nasumično podijeljene u 6 skupina (n = 15) s obzirom na primijenjen tretman. Dio životinja (n = 10) ostavili smo za praćenje parametara; volumen tumora, promjena tjelesne mase životinja, povećanje životnog vijeka i ukupno preživljenje, dok je 5 životinja po skupini žrtvovano 16. dan od inokulacije EAT-a za analizu broja krvnih žila, ekspresiju čimbenika induciranog hipoksijom 1 alfa (HIF-1α) i inducibilne dušik-oksid sintaze (iNOS) te za mjerenje koncentracije dušikovog (II) oksida (NO). Rezultati pokazuju da resveratrol i njegovi nanokristali u kombinaciji s cisplatinom dovode do povećanja životnog vijeka i ukupnog preživljenja miševa, smanjuju volumen tumora kojeg prati smanjenje tjelesne mase životinja. Sama otopina resveratrola snizila je izraženost HIF-1α u tkivu tumora i jetre, dok je izraženost iNOS velika u većini tretiranih grupa što upućuje na protutumorski učinak i aktivnost M1 makrofaga. Resveratrol i njegovi nanokristali, pokazali su i smanjeni broj krvnih žila u tkivu tumora i jetre. Možemo zaključiti da kombinirana primjena resveratrola i cisplatine ima pozitivan učinak u liječenju tumora. Resveratrol i njegovi nanokristali pokazuju antioksidativna, protuupalna i antiangiogena svojstva te osim djelovanja na sam tumor, moguće je da smanjuju toksični učinak cisplatine na jetru.

Abstract (english)

The aim of this study was to investigate the combined effect of a resveratrol solution and its
nanocrystals in a dose of 50 mg/kg ap p lied perorally po and the cisplatin injected
intraperitoneally ( ip in a dose of 2.5 mg/kg, on days 10 and 12, and on day 15 in a dose of 5
mg/kg on the growth of the solid form of Ehrlich ascites tumor (sEAT). A suspension of EAT
cells at a concentration of 1x10 6 was subcutaneously inoculated into the right thigh of Balb/C
mice. The animals were randomly divided into 6 groups (n = 15) according to the applied
treatment. Five animals from each group were sacrificed on the day 16 after EAT inoculation
for the analysis of the number of blood vessels, the expression of hypoxia inducible factor 1
alpha ( HIF 1 α) and inducible nitric oxide synthase ( iNOS), as well as for the measurement of
nitric (II ) oxide (NO) concentrations, while w e kept part of the animals (n = 10) for monitoring
the parameters of tumor volume, change s in animal body weight , increase in lifespan and
overall survival The results indicate that resveratrol and its nanocrystals in combination with
cisplatin lead to an increase in the life span and overall survival of mice, reduce the tumor
volume, which is accompanied by a decrease in the body mass of the animals. The re sveratrol
solution reduced HIF 1 α expression in tumor and liver tissue, while iNOS expression was high
in most of the treated groups, which indicates an antitumor effect and M1 macrophage activity.
Resveratrol and its nanocrystals also showed a reduced number of blood vessels in tumor and
liver tissue. We can conclude that the combined use of resveratrol and cisplatin has a positive
effect in the treatment of tumors. Resveratrol and its nanocrystals show antioxidant, anti
inflammatory and anti angiogenic properties, and besides acting on the tumor itself, it is
possible that they reduce the toxic effect of cisplatin on the liver.

• Keywords: nanokristali; resveratrol; cisplatina; toksičnost; solidni tumor
• Keywords (english): nanocrystals resveratrol; cisplatin; toxicity; solid tumor
• Language: croatian
• URN:NBN: urn:nbn:hr:217:493784
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-12-05
• Created on: 2024-01-11 11:14:54