prikaz prve stranice dokumenta Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša
Embargo period 2025-12-19
doctoral thesis
Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša
Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry, 2023. urn:nbn:hr:163:008050
Ančić, Daniela
University of Zagreb
Faculty of Pharmacy and Biochemistry
Department of pharmaceutical technology

Institutional repository: Repository of Faculty of Pharmacy and Biochemistry University of Zagreb

Cite this document

Ančić, D. (2023). Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:163:008050

Ančić, Daniela. "Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša." Doctoral thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2023. https://urn.nsk.hr/urn:nbn:hr:163:008050

Ančić, Daniela. "Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša." Doctoral thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2023. https://urn.nsk.hr/urn:nbn:hr:163:008050

Ančić, D. (2023). 'Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša', Doctoral thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:163:008050

Ančić D. Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry; 2023 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:163:008050

D. Ančić, "Učinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša", Doctoral thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:163:008050

Metadata
TitleUčinak nanokristala resveratrola na angiogenezu i rast Ehrlichova ascitesnoga i solidnoga tumora u miša
Title (english)Effects of resveratrol nanocrystals on angiogenesis and proliferation of Ehrlich ascites and solid tumour in mice
AuthorDaniela Ančić
MentorNada Oršolić (mentor)
MentorIvan Pepić (komentor)
Committee memberJozsef Petrik (predsjednik povjerenstva)
Committee memberAnita Hafner (član povjerenstva)
Committee memberRanko Stojković (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Pharmacy and Biochemistry
(Department of pharmaceutical technology)
Zagreb
Defense date and country2023-12-19, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Medical Biochemistry
Universal decimal classification
(UDC)		615 - Pharmacology. Therapeutics. Toxicology
Abstract
Resveratrol (3,5,4′-trihidroksi-stilben) jest potencijalan protutumorski spoj zbog svoje antioksidativne, protuupalne, proapoptotičke, antiangiogene i antiproliferativne aktivnosti. Terapijska primjena resveratrola ograničena je njegovim fizikalno-kemijskim i farmakokinetičkim svojstvima. Temeljem navedenog, cilj rada bio je primijeniti resveratrol u obliku nanokristala te istražiti njegov učinak na rast angiogenetski ovisnog, brzo rastućeg Ehrlichovog ascitesnog i solidnog tumora (EAT) te interakciju nanokristala s biološkim tkivom kroz biokemijske i histološke promjene stanica bubrega, jetre i EAT. Rezultati pokazuju da primjena otopine resveratrola (RSV) i suspenzije nanokristala resveratrola (NANO-RSV) dovodi do značajnog smanjenja proliferacije tumorskih stanica u trbušnoj šupljini, te smanjenja broja krvnih žila u potrbušnici, uz nisku sistemsku toksičnost. Prooksidativni učinak resveratrola primijenjenog ip vodi kroničnoj upali, polarizaciji makrofaga od M1 prema M2 fenotipu te skraćenom životnom vijeku nositelja tumora. U histopatološkim ispitivanjima, vidljiva je veća hepatocelularna nekroza i apoptoza, jetrena fibroza oko središnje vene i degeneracija s manjim masnim promjenama u miševa nakon obrade s RSV nego u miševa nakon obrade s NANO-RSV. Primjena RSV i NANO-RSV vodi upali s proksimalnom tubularnom nekrozom i oticanjem bubrežnog glomerula, zajedno s blagim povećanjem biokemijskih parametara kao pokazatelja narušenog funkcionalnog kapaciteta bubrega. Intratumoralna primjena otopine resveratrola i nanokristala resveratrola u solidni EAT pokazala je da dulja nazočnost nanokristala unutar tumorskog tkiva rezultira učinkovitijim antiangiogenim i imunomodulatornim doza-ovisnim učinkom nanokristala u odnosu na otopinu resveratrola te značajno većim preživljenjem nositelja tumora. Sažimajući navedeno, te uzimajući u obzir dobrobit ljudi i ekološku sigurnost, mehanizam toksičnosti resveratrola i njegovih nanokristala potrebno je detaljnije proučiti u cilju boljeg iskorištavanja pozitivnih učinaka nanokristala resveratrola te smanjenja potencijalnih nuspojava njihove terapijske primjene.
Abstract (english)
Resveratrol (3,5,4′ -trihydroxystilbene) is a potential antitumor agent due to its proven anti-oxidative, anti-inflammatory, pro-apoptotic, anti-angiogenic and anti-proliferative properties. Nevertheless, his therapeutic use is limited by its physico-chemical (poor solubility, photo instability) and pharmacokinetic (rapid metabolism and elimination, low bioavailability) properties. The aim of this study was to investigate the potential use of resveratrol (RSV) and its nanocrystals (NANO-RSV) as antitumor agents in Ehrlich ascites tumour (EAT)-bearing mice in ascites and solid form and the interaction of nanocrystals with biological tissue through biochemical and histological changes of kidney, liver and EAT cells. The results show that the administration of resveratrol and its nanocrystals lead to significant reductions in the proliferation of tumour cells in the abdominal cavity, and a reduction of the number of blood vessels in the peritoneum, with low systemic toxicity. Due to pro-oxidative effects of resveratrol after ip administration, chronic inflammation, macrophage polarisation from M1 to M2 phenotype as well as shorter lifespan of resveratrol-treated mice was observed. In histopathological examinations, greater hepatocellular necrosis and apoptosis, hepatic fibrosis around the central vein and degeneration with minor fatty change were observed with RSV than with NANORSV. Inflammation with proximal tubular necrosis and renal glomerulus swelling were also observed, together with slight elevation of several biochemical parameters in both the RSV and NANO-RSV groups. Intra-tumoral administration of RSV and NANO-RSV showed that longer presence of nanocrystals in the tumor tissue improves anti-angiogenic and immunomodulatory dose- depending effects of resveratrol, including overall survival of the mice. With respect for human health and environmental safety, the mechanisms of toxicity require further clarification in order to increase the beneficial effects and reduce the possible risks of therapeutic application of RSV nanocrystals.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:163:008050
Promotion2023
Study programmeTitle: Pharmacy and biochemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor znanosti (doktor znanosti)
Type of resourceText
File originBorn digital
Access conditionsEmbargoed access
Embargo expiration date: 2025-12-19
Terms of useLicence In copyright icon
Created on2024-01-26 11:45:10