Antioxidant Activity and Toxicity of Fullerenols via Bioluminescence Signaling: Role of Oxygen Substituents

Abstract

Fullerenols are nanosized water-soluble polyhydroxylated derivatives of fullerenes, a specific allotropic form of carbon, bioactive compounds, and perspective basis for drug development. Our paper analyzes the antioxidant activity and toxicity of a series of fullerenols with different number of oxygen substituents. Two groups of fullerenols were under investigation: (1) C60Oy(OH)x, C60,70Oy(OH)x, where x+y = 24–28 and (2) C60,70Oy(OH)x, Fe0,5C60Oy(OH)x, Gd@C82Oy(OH)x, where x+y = 40–42. Bioluminescent cellular and enzymatic assays (luminous marine bacteria and their enzymatic reactions, respectively) were applied to monitor toxicity in the model fullerenol solutions and bioluminescence was applied as a signaling physiological parameter. The inhibiting concentrations of the fullerenols were determined, revealing the fullerenols’ toxic effects. Antioxidant fullerenol’ ability was studied in solutions of model oxidizer, 1,4-benzoquinone, and detoxification coefficients of general and oxidative types (DGT and DOxT) were calculated. All fullerenols produced toxic effect at high concentrations (>0.01 g L−1), while their antioxidant activity was demonstrated at low and ultralow concentrations (<0.001 g L−1). Quantitative toxic and antioxidant characteristics of the fullerenols (effective concentrations, concentration ranges, DGT, and DOxT) were found to depend on the number of oxygen substituents. Lower toxicity and higher antioxidant activity were determined in solutions of fullerenols with fewer oxygen substituents (x+y = 24–28). The differences in fullerenol properties were attributed to their catalytic activity due to reversible electron acceptance, radical trapping, and balance of reactive oxygen species in aqueous solutions. The results provide pharmaceutical sciences with a basis for selection of carbon nanoparticles with appropriate toxic and antioxidant characteristics. Based on the results, we recommend, to reduce the toxicity of prospective endohedral gadolinium-fullerenol preparations Gd@C82Oy(OH)x, decreasing the number of oxygen groups to x+y = 24–28. The potential of bioluminescence methods to compare toxic and antioxidant characteristics of carbon nanostructures were demonstrated.

Monitoring of Low-Intensity Exposures via Luminescent Bioassays of Different Complexity: Cells, Enzyme Reactions, and Fluorescent Proteins

“…Hypothetical structures of HS [94] and F are presented in Figure 10. The antioxidant activity of HS was studied in [12,95,96,97,98] and that of F s in [98,99,100,101].…”

“…The latter appears in the presence of exogenous oxidizers depending on their redox potential and concentration [31]. Justification for GT and OxT application to evaluate the toxicity of bioactive compounds was presented in [12,95,96,97,98,99,100,101].…”

“…Toxic concentrations of HS and F inhibiting bioluminescence were determined as >0.002 g/L and >0.01 g/L, respectively. Bacterial bioluminescent assay demonstrated the following toxic intervals: >0.1 g/L and >0.01 g/L for HS [96] and F [101], respectively. All toxic concentrations were excluded from the further antioxidant experiments.…”

“…In [98,101], the antioxidant activity of F s was related with modifications of their surface by oxygen substituents, as well as the presence of exo- or endohedral metal atoms. Differences in the antioxidant activity of these F s were explained through their electron donor/acceptor properties and differences in catalytic activity.…”

Effects of Modified Magnetite Nanoparticles on Bacterial Cells and Enzyme Reactions

“…To evaluate molecular mechanisms of possible biological effects of the MNPs, enzymatic bioassays can be applied. The bioluminescence enzymatic assay is a relatively new direction in a toxicology practice [ 42 , 43 , 44 ]. The conventional enzymatic bioluminescent assay is based on the bacterial bioluminescent enzyme system, which involves two coupled enzymatic reactions: …”