Antioxidant Properties of Fullerene Derivatives Depend on Their Chemical Structure: A Study of Two Fullerene Derivatives on HELFs.

Vasilina Sergeeva,Svetlana Kostyuk,Elizaveta Ershova,Pavel Troshin,Sergei Kutsev,Olga Kraevaya,Elena Malinovskaya,Larisa Kameneva,Alexander Zhilenkov,Iliya Voronov,Marina Konkova,Olga Dolgikh,Natalia Veiko

doi:10.1155/2019/4398695

Abstract

Oxidative stress is a major issue in a wide number of pathologies (neurodegenerative, cardiovascular, immune diseases, and cancer). Because of this, the search for new antioxidants is an important issue. One of the potential antioxidants that has been enthusiastically discussed in the past twenty years is fullerene and its derivatives. Although in aqueous solutions fullerene derivatives have shown to be antioxidants, their properties in this regard within the cells are controversially discussed. We have studied two different water-soluble fullerene C60 and C70 derivatives on human embryonic lung fibroblasts at a wide range of concentrations. Both of them cause a decrease in cellular ROS at short times of incubation (1 hour). Their prolonged action, however, is fundamentally different: derivative GI-761 causes secondary oxidative stress whereas derivative VI-419-P3K keeps ROS levels under control values. To gain a better understanding of this effect, we assessed factors that could play a role in the response of cells to fullerene derivatives. Increased ROS production occurred due to NOX4 upregulation by GI-761. Derivative VI-419-P3K activated the transcription of antioxidant master regulator NRF2 and caused its translocation to the nucleus. This data suggests that the antioxidant effect of fullerene derivatives depends on their chemical structure.

Highlights

Oxidative stress plays an important role in various diseases (Alzheimer’s disease, schizophrenia, rheumatoid arthritis, diabetes, cardiovascular diseases, and cancer) and ageing [1,2,3]
reactive oxygen species (ROS) production level was measured with the DCF reagent in a plate reader (EnSpire, Finland)
The results are shown as a ratio of ki/k0, where ki is the inclination for the time and concentration of interest and k0 is the inclination in control cells

Summary

Introduction

Oxidative stress plays an important role in various diseases (Alzheimer’s disease, schizophrenia, rheumatoid arthritis, diabetes, cardiovascular diseases, and cancer) and ageing [1,2,3]. Increased amounts of ROS lead to DNA damage, oxidative stress, and cell death [5,6,7]; novel antioxidants are of interest. One of the synthetic antioxidants that gained a lot of attention in the past decades is fullerene and its derivatives. It has been shown that fullerene derivatives act as strong antioxidants in solutions, the data concerning their antioxidant properties on cell cultures is controversial. Some studies confirm the antioxidative action of fullerenes whereas others show that cells treated with fullerenes exhibit signs of oxidative stress

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Results

Conclusion