Abstract
Hydroxylated fullerenes are reported to be very strong antioxidants, acting to quench reactive oxygen species, thus having strong potential for important and widespread applications in innovative therapies for a variety of disease processes. However, their potential for toxicological side effects is still largely controversial and unknown. Effects of hydroxylated fullerenes C60(OH)24 on the fathead minnow (Pimephales promelas) were investigated microscopically after a 72-hour (acute) exposure by intraperitoneal injection of 20 ppm of hydroxylated fullerenes per gram of body mass. Cumulative, semi-quantitative histopathologic evaluation of brain, liver, anterior kidney, posterior kidney, skin, coelom, gills and the vestibuloauditory system revealed significant differences between control and hydroxylated fullerene-treated fish. Fullerene-treated fish had much higher cumulative histopathology scores. Histopathologic changes included loss of cellularity in the interstitium of the kidney, a primary site of haematopoiesis in fish, and loss of intracytoplasmic glycogen in liver. In the coelom, variable numbers of leukocytes, including many macrophages and fewer heterophils and rodlet cells, were admixed with the nanomaterial. These findings raise concern about in vivo administration of hydroxylated fullerenes in experimental drugs and procedures in human medicine, and should be investigated in more detail.
Highlights
Hydroxylated fullerenes are de facto nanoparticles with primary particle size of 1 nm, made soluble in water by the introduction of hydroxyl groups to C60 molecule during their preparation (Kokubo 2012)
Due to their intrinsic properties, hydroxylated fullerenes act as potent, non-selective antioxidant agents and can intercept and quench all of the physiologically relevant reactive oxygen species (ROS) (Ueng et al 1997; Markovic & Trajkovic 2008; Yin et al 2009)
C60(OH)24 hydroxylated fullerenes are being investigated as experimental drugs in the treatment of Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (Cai et al 2008; Cataldo & da Ros 2008; Dugan et al 2001), as well as in other therapeutic and diagnostic purposes such as anti-cancer/tumour/ proliferative/metastatic/bacterial and antiviral agents (Bogdanovic et al 2004; Cataldo & da Ros 2008, Kokubo 2012)
Summary
Hydroxylated fullerenes (fullerenols) are de facto nanoparticles with primary particle size of 1 nm, made soluble in water by the introduction of hydroxyl groups to C60 molecule during their preparation (Kokubo 2012). Readily soluble in water due to hydroxyl groups, the large fullerenol hydrophobic core and p–p interactions are responsible for formation of nanoparticle aggregates with a size range of 20–450 nm (Kokubo 2012) Due to their intrinsic properties, hydroxylated fullerenes act as potent, non-selective antioxidant agents and can intercept and quench all of the physiologically relevant reactive oxygen species (ROS) (Ueng et al 1997; Markovic & Trajkovic 2008; Yin et al 2009). Differences in surface modification, i.e., hydroxylation, are likely to contribute to differences in results obtained from various studies These recent studies have raised concerns about the potential toxicity of C60(OH) as, to a certain extent, the properties which benefit some biomedical functions may damage others as side effects. The ability of C60(OH) to prevent mitochondrial dysfunction and oxidative damage in an MPP+-induced cellular model of Parkinson’s disease (Cai et al 2008) can cause mitochondrial arrest and depletion of ATP (Johnson-Lyles et al 2010) with serious consequences
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