Genotoksični učinci hipertermije, citostatika cisplatine i kvercetina na zdrave i tumorske stanice miša

master's thesis

• Title (english): Genotoxic effects of hyperthermia, cytostatic cisplatin and quercetin on normal and tumour cells in mice
• Author: Martina Kunštić
• Mentor: Nada Oršolić (mentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Ines Radanović (član povjerenstva)
• Committee member: Dubravka Matković-Čalogović (član povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2010, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Bioflavonoid kvercetin je polifenolni spoj široko rasprostranjen u biljnom svijetu, poznat po svojim antioksidativnim, protutumorskim, imunomodulatorskim i protuupalnim svojstvima. Također je dokazano da djeluje kao senzibilizator hipertermije povećavajući apoptozu u različitim linijama tumorskih stanica in virto i in vivo. Cilj ovog istraživanja bio je pratiti procjenu protutumorske, genotoksične i imunomodulatorske učinkovitosti citostatika cisplatine i/ili imunomodulatora kvercetina sa i bez primjene hipertemije na miševe nositelje Ehrlichova ascitescnog tumora (EAT-a) metodom alkalnog komet testa. Miševe soja Swiss albino preventivno smo obradili intraperitonealno (i.p.) pripravkom kvercetina (50 mg kg-1) 7. i 3. dana prije i.p. unosa 2x106 EAT stanica. Kemoterapiju (37°C) i hipertermičku kemoterapiju (43°C) s citostatikom cisplatinom (5 ili 10 mg kg-1) primijenili smo 3. dan nakon injiciranja tumorskih stanica u peritonealnu šupljinu. Rezultati alkalnog komet testa ukazuju na sinergistički učinak hipertermije, kemoterapije te imunoterapije s kvercetinom u povećanoj zaštiti molekula DNA u leukocitima, hepatocitima i stanicama bubrega od oštećenja uzrokovanih toksičnim metabolitima cisplatine. Imunomodulacija kvercetinom te smanjena toksičnost citostatika cisplatine s kvercetinom vjerojatno je mogući mehanizam protutumorske učinkovitosti. Analizom rezultata zaključili smo da kvercetin združen s citostatikom ciplatinom može povećati protutumorski učinak kemoterapeutika, što sugerira moguću kliničku upotrebu u cilju povećanja imunosti organizma te smanjenja štetnih učinaka toksičnih metabolita citostatika cisplatine na zdrave stanice i tkiva.

Abstract (english)

The bioflavonoid quercetin, a polyphenolic compound widely distributed in the plant kingdom, is known to its antioxidative, antitumour, immunomodulative, and anti-inflamatory properties. It also has been shown to act as a hyperthermia sensitizer by increasing the apoptosis in a variety of tumour cell lines both in vitro and in vivo. The aim of this study was to explore and compare antitumour, genotoxic and immunomodulatory effects of cytostatic cisplatin and/or immunomodulator quercetin with and without hyperthermia in mice-bearing Ehrlich ascites tumour (EAT) using the method of alkaline comet assay. In Swiss albino mice preventively treated intraperitoneally (i.p.) by quercetin (50 mg kg-1) on the 7th and 3rd day before i.p. injection of 2x106 EAT cells. Chemotherapy (37°C) and hypothermical chemotherapy (43°C) with cisplatin (5 or 10 mg kg-1) were given on the 3rd day after the tumour cell injection into the abdominal cavity of mice. These results of alkaline comet assay suggest the synergistic effect of hyperthermia, chemotherapy and immunotherapy with quercetin in increased DNA protection of leukocytes, hepatocytes and kidney cells from damages caused by toxic metabolites of cispaltin. It is likely that immunomodulation of quercetin and reducing toxicity of chemotherapy treatment with quercetin may be possible mechanism of antitumour efficiency. The analisys of the results has led us to the conclusion that the combination of quercetin with cytostatic cisplatin could increase the antitumour potential of chemoterapeutic agents which suggests the benefits of potential clinical use in order to maximize immunity of organism and minimize harmful effects of toxic metabolites of cytostatic cisplatin on normal cells and tissues.

• Keywords: kvercetin; cisplatina; hipertermija; Ehrlichov ascitesni tumor; komet test
• Keywords (english): quercetin; cisplatin; hypethermia; Ehrlich ascites tumour; comet assay
• Language: croatian
• URN:NBN: urn:nbn:hr:217:185216
• Study programme: Title: Biology and Chemistry; Study programme type: university; Study level: graduate; Academic / professional title: profesor biologije i kemije (profesor biologije i kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-27 10:56:11