Beuerle, Florian and Witte, Patrick and Hartnagel, Uwe and Lebovitz, Russell and Parng, Chuenlei and Hirsch, Andreas (2007) Cytoprotective activities of water-soluble fullerenes in zebrafish models. JOURNAL OF EXPERIMENTAL NANOSCIENCE, 2 (3). pp. 144-170.
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Using zebrafish (Danio rerio) embryos as a model system, we compared the antioxidant and cytoprotective effects of a series of new water-soluble fullerenes 1-12. Since zebrafish embryos are transparent during the first week of life, the effects of fullerenes on multiple organ systems, including CNS, PNS, and heart, could be assessed in situ. Both positively charged and negatively charged water-soluble fullerenes were added at concentrations between 1 and 500 mu M to 96 well plates containing zebrafish embryos at 24-120 hours post fertilization (hpf). Direct toxicity of each fullerene compound was assessed by LC50. In addition, we assessed the ability of each fullerene to protect against toxicity induced by known chemical toxins in this system. Four different drug/chemical toxicity models were used in our study: (i) protection of neuromast hair cells from gentamicin-induced toxicity; (ii) protection of neuromast hair cells from cisplatinum-induced toxicity; (iii) protection of tyrosine hydroxylase-containing dopaminergic CNS neurons from 6-hydroxydopamine toxicity; and (iv) protection of total CNS neurons from 6-hydroxydopamine toxicity. Our results indicate that (i) positively charged water-soluble fullerenes tend to exhibit greater toxicity than negatively charged fullerenes with similar structures; (ii) toxicity varies considerably among negatively charged fullerenes from very low to moderate, depending on structural features; (iii) dendrofullerenes 2-7 (monoadducts of C-60) show stronger protection against cisplatinum toxicity in neuromast hair cells while then the e, e, e-trismalonic acid 1 (so called C3) shows stronger protection against gentamicin-induced cytotoxicity in the same cells; (iv) C3 (1) is relatively unstable in all aqueous solvents tested and breaks down mainly through decarboxylation reactions to form penta, tetra and tris carboxylated forms, which exhibit increased toxicity in vivo compared with C3 (1). Our findings indicate that water-soluble fullerenes can protect against chemical toxin-induced apoptotic cell death in a vertebrate, whole-animal model that may be useful for predicting the efficacy and toxicity of these compounds in mammals. Furthermore, the relative potential for pharmacologic use of these compounds varies considerably with respect to stability.
|Uncontrolled Keywords:||fullerenes; dendrimers; antioxidants; superoxide; neuroprotection; otoprotection|
|Subjects:||Material Science > Functional and hybrid materials|
NanoSafety > Environment, health and safety aspects of nanotechnology
|Deposited By:||Farnush Anwar|
|Deposited On:||13 Jan 2009 11:49|
|Last Modified:||31 Mar 2009 15:48|
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