Mehanizam antiagregacijskog učinka flavanona

master's thesis

• Title (english): Mechanism of antiaggregatory effect of flavanones
• Author: Dobrila Blagaić
• Mentor: Mirza Bojić (mentor)
• Committee member: Mirza Bojić (predsjednik povjerenstva)
• Committee member: Željan Maleš (član povjerenstva)
• Committee member: Renata Jurišić Grubešić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2016-07-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Flavonoidi su velika skupina spojeva biljnog porijekla i široko su rasprostranjeni u prirodi. Osnovna struktura im je zajednička, a razlikuju se po supstituentima. Mnogima od njih pripisuju se antioksidativni, antibakterijski, antivirusni, citostatički, analgetski i drugi učinci. U ovom radu proučavalo se njihovo antiagregacijsko djelovanje.
Iako je agregacija trombocita fiziološki odgovor na ozljedu, pretjerana agregacija je jedan od uzroka pogoršanja kardivaskularnih bolesti. Acetilsalicilna kiselina i klopidogrel se kod današnjih pacijenata uvode u terapiju kao preventiva kardiovaskularnim oboljenjima. Ta dva lijeka, uz svoj terapijski učinak, imaju i određene nuspojave zbog čega se nesprestano traga za novim alternativama. Sve više istraživanja danas se okreće prirodnim izvorima pa su tako i flavonoidi zbog svojih mnogobrojnih učinaka postali predmet istraživanja.
Ispitan je antiagregacijski učinak 6-hidroksiflavona jer se on u prethodnim istraživanjima pokazao kao jak antiagregacijski agens. Korištena je impedancijska agregometrija, a rezultat je iskazan kao MINaAC, minimalna koncentracija flavonoida koja uzrokuje statistički značajno smanjenje agregacije trombocita. Kao induktori agregacije korišteni su ADP, arahidonska kiselina i kolagen. Izmjerena MINaAC kod sva tri induktora je u rangu koncentracija flavonoida koja se može postići in vivo.
6-hidroksiflavon zbog svega navedenog posjeduje potencijal kliničke primjene, iako su potrebna dodatna istraživanja s drugim induktorima agregacije. Nadalje, 6-hidroksiflavon može utjecati i na laboratorijske pretrage funkcije trombocita. Primjerice, ako pacijent konzumira hranu bogatu flavonoidima liječnik može pogriješiti u optimiranju terapije zbog interferencije flavonoida na stvarne parametre funkcije trombocita.

Abstract (english)

Flavonoids are a large group of substances of plant origin and are widely distributed in nature. They have common basic structure and are distinguished by present substituens. Some of them have positive effects on organism e.g. antioxidative, antibacterial, antiviral, cytostatic, analgetic etc. In this thesis the antiaggregatory effect of 6-hydroxyflavone was studied.
Although platelet aggregation is a physiological response to injury, excess aggregation is one of the major causes of cardiovascular diseases. Aspirin and clopidogrel are often used in prevention of cardiovascular diseases. These two drugs, along with their therapeutic effect have some side effects, thus the search for novel drugs continues. Today more and more researches are focused on natural substances. Therefore, the flavonoids have become research target because of its various beneficial effects.
Antiaggregatory effect of 6-hydroxyflavone was tested because it has proved to be strong antiaggregatory agent. Method used for functional analysis of thrombocites was impedance aggregometry and results were shown as minimal flavonoid concentration which significantly reduces aggregation (MINaAC). ADP, arachidonic acid and collagen were used as inducers of aggregation. Detected MINaAC with all three inducers are possible in vivo.
6-hydroxyflavone has a potential of clinical use, although experiments with other inducers of aggregation is required. Thereover, 6-hydroxyflavone can alter laboratory results of platelet function. If flavonoid rich food is consumed, physician can incorrectly estimate platelet function and prescribe non-optimal therapy.

• Keywords: adenozin-difosfat; arahidonska kiselina; kolagen; agregacija trombocita; 6-hidroksiflavon
• Keywords (english): adenosine diphosphate; arachidonic acid; collagen; aggregation of platelets; 6-hydroxyflavone
• Language: croatian
• URN:NBN: urn:nbn:hr:163:582713
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2018-10-04 14:46:10