Ispitivanje efekata hronične primene cisplatine i ru(II) kompleksa na izolovano srce i oksidacioni stres pacova
Investigation of the effects of chronic administration of cisplatin and Ru(II) complexes on the isolated heart and oxidative stress of rats
Doktorand
Radonjić, KatarinaMentor
Novokmet, SlobodanČlanovi komisije
Jakovljević, VladimirĐurić, Dragan
Jeremić, Jovana
Metapodaci
Prikaz svih podataka o disertacijiSažetak
Uvod: Kompleksi rutenijuma(II) su pokazali antitumorsku aktivnost, a njihova
prednost u poređenju sa cisplatinom ogleda se u potencijalno nižoj toksičnosti,
dobroj selektivnosti i inhibiciji metastaza.
Cilj: Cilj ove studije bio je da se ispitaju efekti kompleksa rutenijuma, [Ru(Cltpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl] i [Ru(Cl-tpy)(bpy)Cl][Cl], na srce i uporede sa
cisplatinom. Posebna pažnja je bila usmerena i ka ispitivanju efekata cisplatine i
kompleksa rutenijuma na indukciju oksidacionog stresa.
Materijal i metode: U studiju je bilo uključeno 60 W. albino pacova podeljenih u 5
grupa. Životinje su 4 nedelje primale 4 mg/kg/nedeljno komplekse rutenijuma, i
cisplatinu u istoj dozi i fiziološki rastvor (4 ml/kg). Na kraju tretmana, životinje
su žrtvovane, a srca su perfundovana prema Langendorff-ovom modelu. U krvi se
određivao nivo markera oksidacionog stresa i funkcije srca, bubrega i jetre.
Rezultati: [Ru(Cl-tpy)(en)Cl][Cl] je ispoljio negativno inotropno i hipotenziv...no
dejstvo i indukovao oksidacioni stres, slično kao i cisplatina, dok su
histopatološka oštećenja organa bila blaža. [Ru(Cl-tpy)(dach)Cl][Cl] je ostvario
negativno inotropno i hipotenzivno dejstvo i snažan oksidacioni stres, i ova
dejstva su bila slabija od cisplatine. [Ru(Cl-tpy)(bpy)Cl][Cl] je ostvario slične
efekte na srce kao i [Ru(Cl-tpy)(dach)Cl][Cl] i indukovao umereni oksidacioni stres.
Zaključak: Profil toksičnosti [Ru(Cl-tpy)(en)Cl][Cl] smanjuje izglede za
potencijalnu terapijsku primenu, dok bi [Ru(Cl-tpy)(dach)Cl][Cl] i [Ru(Cltpy)(bpy)Cl][Cl] mogli biti potencijalni kandidati za dalji razvoj, uz hemijske
modifikacije koje bi umanjile toksičnost, a povećale biološku aktivnost.
Introduction: Ruthenium(II) complexes have shown antitumor activity and their advantage
compared to cisplatin is reflected in potentially lower toxicity, good selectivity and inhibition
of metastases.
Aim: The aim of this study was to examine the effects of ruthenium complexes, [Ru(Cltpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl] and [Ru(Cl-tpy)(bpy)Cl][Cl], on heart and
compared with cisplatin. Special attention was aimed at examining the effects of cisplatin and
ruthenium complexes on induction of oxidative stress.
Material and methods: 60 W. albino rats divided into 5 groups were included in study.
Animals received 4 mg/kg/week of ruthenium complexes, and cisplatin in same dose and
physiological solution (4 ml/kg) for 4 weeks. At the end of treatment animals were sacrificed
and hearts were perfused according to Langendorff model. The level of markers of oxidative
stress and heart, kidney and liver function was assessed in blood.
Results: [Ru(Cl-tpy)(en)Cl][Cl] exerted negative in...otropic and hypotensive effects and
induced oxidative stress, similar to cisplatin, while histopathological organ damage was
milder. [Ru(Cl-tpy)(dach)Cl][Cl] exerted negative inotropic and hypotensive effects and
strong oxidative stress, and these effects were weaker than cisplatin. [Ru(Cl-tpy)(bpy)Cl][Cl]
exerted similar cardiac effects as [Ru(Cl-tpy)(dach)Cl][Cl] and induced moderate oxidative
stress.
Conclusion: The toxicity profile of [Ru(Cl-tpy)(en)Cl][Cl] reduces the prospects for potential
therapeutic use, while [Ru(Cl-tpy)(dach)Cl][Cl] and [Ru(Cl-tpy)(bpy)Cl][Cl] could be
potential candidates for further development, with chemical modifications that would reduce toxicity and increase biological activity.