Naslov (srp)

Ispitivanje efekata hronične primene cisplatine i ru(ii) kompleksa na izolovano srce i oksidacioni stres pacova

Autor

Radonjić, Katarina, 1987-

Doprinosi

Novokmet, Slobodan, 1970-
Jakovljević, Vladimir, 1971-
Đurić, Dragan, 1961-
Jeremić, Jovana, 1991-

Opis (eng)

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 inotropic 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.

Opis (srp)

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 hipotenzivno 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.

Opis (srp)

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Jezik

srpski

Datum

2022

Licenca

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Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode