1685P - Fullerenol/iron nanocomposite modulates doxorubicin-induced cardiotoxicity

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Complications of Treatment
Translational Research
Presenter Mariana Seke
Citation Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390
Authors M. Seke1, D. Petrovic2, M. Labudovic Borovic3, D. Jović4, I. Borisev4, Z. Kanacki5, D. Zikic5, A. Djordjevic4
  • 1Department Of Radiobiology And Molecular Genetics, Institute of Nuclear Research VINCA, 11001 - Belgrade/RS
  • 22department Of Natural Sciences And Mathematics, Faculty of Education Sombor, University of Novi Sad, 25000 - Sombor/RS
  • 3Department Of Pathology, Institute of Histology and Embryology "Aleksandar Dj. Kostic", Faculty of Medicine, University of Belgrade, 11000 - Belgrade/RS
  • 4Department Of Chemistry, Biochemistry And Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000 - Novi Sad/RS
  • 5Department Of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, 21000 - Novi Sad/RS

Abstract

Background

Doxorubicin is a first line cancer chemotherapeutic. Unfortunately, its clinical use is limited by its cardiotoxicity. It is known that iron overload aggravates anthracycline toxicity. Fullerenol is a 1 nm size molecule and in aqueous solutions is in the form of polyanionic nanoparticles, which enables them to serve as a good carrier of positively charged ions such as Fe2+. Fullerenol’s antioxidant activity through scavenging free radicals has already been proved in different biological systems.

Methods

The aim of our study was to investigate the effects of the fullerenol/iron nanocomposite as a pretreatment to doxorubicin on the rat’s heart in comparison to doxorubicin alone. After the 24h-treatment, adult male Wistar rats were sacrificed and hearts were collected for ultrastructural and qRT-PCR analysis. Considering the ability of doxorubicin to induce oxidative stress, and the fullerenol’s capability to mitigate it, we had chosen to monitor gene expression of enzymes involved in antioxidant defense.

Results

Ultrastructural study revealed that in the group pretreated with the nanocomposite prior to doxorubicin application cardiomyocytes were with preserved morphology and the structure of intercalated discs. On the other hand, the heart tissues of animals treated with doxorubicin alone were significantly more damaged. Intensive interstitial edema was observed, as well as vacuolization of cardiomyocytes, hypercontraction of sarcomeres, mitochondria of irregular shapes. qRT-PCR results have shown that neither treatment with doxorubicin alone nor the pretreatment with the nanocomposite did cause significant increase in mRNA levels of catalase and superoxide dismutase.

Conclusions

Our results indicate that the fullerenol/iron nanocomposite applied as pretreatment to doxorubicin induces less damage to the hearth tissue in comparison to doxorubicin alone.

Clinical trial identification

Legal entity responsible for the study

Aleksandar Djordjevic

Funding

Ministry of Education, Science and Technological Development, Republic of Serbia, Grant No. III 45005.

Disclosure

All authors have declared no conflicts of interest.