Cytoprotective Activities of Water-Soluble Fullerenes in Zebrafish Models - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 260

Table 19.2 LC 50 of Fullerenes 1-12 in Zebrafish

Compound Class LC 50 zebrafish (mM)

1 C3-like fullerenes 596

2 Dendrofullerenes

> 500 (30% lethality at 500 mM)

3 Dendrofullerenes

> 500 (20% lethality at 500 mM)

4 Dendrofullerenes ND

5 Dendrofullerenes ND

6 Dendrofullerenes 250 (0% lethality at 250 mM)

7 Dendrofullerenes ND

8 C3-like fullerenes 500 (0% lethality at 250 mM)

9 C3-like fullerenes 500 (0% lethality at 250 mM)

10 C3-like fullerenes 117

11 Oxo-aminofullerenes 104

12 Oxo-aminofullerenes 30

values up to 0% lethality at 500 M for 8 and 9. In several cases, morphological

abnormalities such as shortened body length and abnormal body curvature were
detected in embryos treated with fullerene concentrations at or near the LC 50 .For
example, we observed shortened body length after treatment with C3 (1) at 250

m

m M

(Fig. 19.4a, panel B) and slight curvature of the body after treatment with 3 at 500 M

(Fig. 19.4a, panel C). The majority of fullerenes tested showed no observable body
length or curvature abnormalities (see, for example, Fig. 19.4b). Higher resolution
microscopy of individual organs within developing zebrafish embryos showed
abnormal cardiac chambers in the presence of 250

m

MC3(1) (Fig. 19.5b), enlarge-
ment of liver and intestines in the presence of 3 at 500

m

m M (Fig. 19.5c), and

underdevelopment of liver and intestines in the presence of 2 at 500 m M

(Fig. 19.5f). In addition, embryos treated with 8 (500 M) showed slight enlargement

of the heart (Fig. 19.5h). These results suggest that at high concentrations, some
water-soluble fullerenes may exhibit teratogenic effects, but this has not yet been
tested in mammals.
The decarboxylation breakdown products of C3 (1) represent an important
exception with respect to our generalization of low toxicity for anionic fullerenes.
With progressive decarboxylation steps, each resulting C3 breakdown product
shows increasing toxicity with respect to the parent C3 (1) (Table 19.3). The LC 50
for C3 (1) is 596

m

m M, followed by C3-penta at 373 m M, C3-tetra at 134 m M, and C3-

tris at 10 M. Interestingly, the increasing toxicity of the progressive C3 decar-

boxylation products was not observed with cultured murine endothelial cells, at
least for C3-tris (data not shown), suggesting that the toxic effects of C3 decar-
boxylation products may be limited to a specific cell, tissue, or organ type that is
critical for overall survival. To further investigate this possibility, we initiated a
series of experiments to study the effects of C3 (1) and its decarboxylated

m