Molecular and Cellular Biochemistry

, Volume 439, Issue 1–2, pp 19–33 | Cite as

Cisplatin and cisplatin analogues perfusion through isolated rat heart: the effects of acute application on oxidative stress biomarkers

  • Isidora M. Stojic
  • Vladimir I. Zivkovic
  • Ivan M. Srejovic
  • Tamara R. Nikolic
  • Nevena S. Jeremic
  • Jovana N. Jeremic
  • Dragan M. Djuric
  • Nemanja Jovicic
  • Katarina G. Radonjic
  • Zivadin D. Bugarcic
  • Vladimir L. J. JakovljevicEmail author
  • Slobodan S. Novokmet


Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its’ analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2′:6′,2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10−6 and 10−5 M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2′:6′,2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2′:6′,2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.


Oxidative stress Cisplatin Cisplatin analogues Isolated perfused rat heart 


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Isidora M. Stojic
    • 1
  • Vladimir I. Zivkovic
    • 2
  • Ivan M. Srejovic
    • 2
  • Tamara R. Nikolic
    • 1
  • Nevena S. Jeremic
    • 1
  • Jovana N. Jeremic
    • 1
  • Dragan M. Djuric
    • 3
  • Nemanja Jovicic
    • 4
  • Katarina G. Radonjic
    • 1
  • Zivadin D. Bugarcic
    • 5
  • Vladimir L. J. Jakovljevic
    • 2
    • 6
    Email author
  • Slobodan S. Novokmet
    • 1
  1. 1.Department of Pharmacy, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  2. 2.Department of Physiology, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  3. 3.Institute of Medical Physiology “Richard Burian” Faculty of MedicineUniversity of BelgradeBelgradeSerbia
  4. 4.Department of Histology and Embriology, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  5. 5.Department of Chemistry, Faculty of ScienceUniversity of KragujevacKragujevacSerbia
  6. 6.Department of Human PathologyI.M. Sechenov First Moscow State Medical UniversityMoscowRussia

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