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.
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.
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.
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
Ministry of Education, Science and Technological Development, Republic of Serbia, Grant No. III 45005.
All authors have declared no conflicts of interest.