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Title: Redox and apoptotic potential of novel ruthenium complexes in rat blood and heart
Authors: Mihajlović K.
Milosavljevic I.
Jeremic, Jovana
Savic M.
Sretenovic J.
Srejovic I.
Zivkovic V.
Jovicic, Nemanja
Paunović, Milica
Bolevich, Sergey
Jakovljevic V.
Novokmet, Slobodan
Journal: Canadian Journal of Physiology and Pharmacology
Issue Date: 1-Jan-2021
Abstract: © 2021, Canadian Science Publishing. All rights reserved. Ruthenium(II) complexes offer the potential for lower toxicity compared with platinum(II) complexes. Our study aimed to compare cardiotoxicity of [Ru(Cl-tpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl], [Ru(Cl-tpy)(bpy)Cl][Cl], cisplatin, and saline through assessment of redox status and relative expression of apoptosis-related genes. A total of 40 Wistar albino rats were divided into five groups. Ruthenium groups received a single dose of complexes intraperitoneally (4 mg/kg/week) for a 4-week period; cisplatin group received cisplatin (4 mg/kg/week) and control group received saline (4 mL/kg/week) in the same manner as ruthenium groups. In collected blood and heart tissue samples, spectrophotometric determination of oxidative stress biomarkers was performed. The relative expression of apoptosis-related genes (Bcl-2, Bax, and caspase-3) in hearts was examined by real-time polymerase chain reaction. Our results showed that systemic and cardiac pro-oxidative markers (thiobarbituric acid reactive substances and nitrite) were significantly lower in ruthenium groups compared with cisplatin group, while concentrations of antioxidative parameters (catalase, superoxide dismutase, and oxidized glutathi-one) were significantly higher. Ruthenium administration led to significantly lower gene expression of Bax and caspase-3 compared with cisplatin-treated rats, while Bcl-2 remained unchanged. Applied ruthenium complexes have less pronounced potential for induction of oxidative stress-mediated cardiotoxicity compared with cisplatin. These findings may help for future studies that should clarify the mechanisms of cardiotoxicity of ruthenium-based metallodrugs.
Type: Article
DOI: 10.1139/cjpp-2020-0349
ISSN: 00084212
SCOPUS: 85101831352
Appears in Collections:Faculty of Medical Sciences, Kragujevac
Faculty of Science, Kragujevac
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