Utjecaj različitih formulacija doksorubicina na oksidativni stres u jetri

master's thesis

• Title (english): Effect of different doxorubicin formulation on oxidative stress in liver
• Author: Anita Pavišić
• Mentor: Petra Turčić (mentor)
• Committee member: Petra Turčić (predsjednik povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Committee member: Blanka Tariba Lovaković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2020-09-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Doksorubicin je široko korišteni kemoterapeutik i jedan je od najvažnijih antitumorskih lijekova u kliničkoj praksi, međutim njegova primjena ograničena je brojnim nuspojavama koje nastaju zbog njegove neselektivnosti. Osim što uzrokuje kardiomiopatije, doksorubicin štetno djeluje na brojne druge organe, uključujući jetru. Oksidativni stres ima značajnu ulogu u toksičnosti doksorubicina. Zbog važnosti doksorubicina u antitumorskoj terapiji, vrlo je važno istražiti strategije za poboljšanje terapijskog indeksa, posebno smanjenjem incidencije i jačine njegove toksičnosti. Razvoj inovativnih formulacija jedna je od strategija za razvoj djelotvornijih terapija protiv raka. Primjena nanoformulacija ima veliki potencijal za učinkovitiju isporuku lijekova, poboljšanje terapijske učinkovitosti te smanjenje nuspojava. U ovom radu ispitano je kako primjena inovativne nanoformulacije doksorubicina utječe na parametre oksidativnog stresa u jetri mužjaka i ženki štakora u usporedbi s konvencionalnim doksorubicinom i liposomalnom fromulacijom Myocet koji su već odobreni za kliničku primjenu te su ispitane razlike u učinku različitih formulacija doksorubicina na životinje različitog spola. Uz kontrolu za spol, tretman konvencionalnim doksorubicinom uzrokovao je najveći porast razine mjerenih parametara oksidativnog stresa u usporedbi s liposomalnom i nanoformulacijom doksorubicina te je kod svih ispitivanih parametara oksidativnog stresa, uz kontrolu za tretman, uočena je značajna razlika između mužjaka i ženki. Mužjaci su, u odnosu na ženke, imali višu razinu svih ispitivanih parametara kod svih pokusnih skupina, osim razine reduciranog glutationa i superoksidnog radikala za skupine tretirane PLGADox-om.

Abstract (english)

Doxorubicin is a widely used chemotherapeutic agent and is one of the most important antitumor drugs in clinical practice, but owing to its number of side effects, caused mainly by its low selectivity, its clinical use has been limited. In addition to causing cardiomyopathies, doxorubicin is harmful to many other organs, including the liver. Oxidative stress plays a significant role in doxorubicin toxicity. Due to the importance of doxorubicin in antitumor therapy, it is very important to investigate strategies to improve the therapeutic index, especially by reducing the incidence and severity of its toxicity. The development of innovative formulations is one of the strategies for developing more effective cancer therapies. Use of nanoformulations has great potential for more efficient drug delivery, improvement of therapeutic efficacy and reduction of side effects. In this study, it was investigated how the application of the innovative nanoformulation of doxorubicin affects the parameters of oxidative stress in the liver of male and female rats compared with conventional doxorubicin and liposomal formulation Myocet that have already been approved for clinical use and differences in the effect of different doxorubicin formulations on animals of different sexes were examined. In addition to gender control, treatment with conventional doxorubicin caused the highest increase in the level of measured oxidative stress parameters compared to liposomal and nanoformulation of doxorubicin and in all examined parameters of oxidative stress, in addition to control for treatment, a significant difference was observed between males and females. Males, compared to females, had higher levels of all examined parameters in all experimental groups, except the level of reduced glutathione and superoxide radical for the groups treated with PLGADox.

• Keywords: doksorubicin; oksidativni stres; jetra
• Keywords (english): doxorubicin; oxidative stress; liver
• Language: croatian
• URN:NBN: urn:nbn:hr:163:859902
• 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: Open access
• Created on: 2021-11-15 16:51:09