Fullerene C60 exposure elicits an oxidative stress response in embryonic zebrafish

Due to its unique physicochemical and optical properties, C-60 has raised interest in commercialization for a variety of products. While several reports have determined this nanomaterial to act as a powerful antioxidant, many other studies have demonstrated a strong oxidative potential through photoactivation. To directly address the oxidative potential of C-60, the effects of light and chemical supplementation and depletion of glutathione (GSH) on C-60-induced toxicity were evaluated. Embryonic zebrafish were used as a model organism to examine the potential of C-60 to elicit oxidative stress responses. Reduced light during C-60 exposure significantly decreased mortality and the incidence of fin malformations and pericardial edema at 200 and 300 ppb C-60. Embryos co-exposed to the glutathione precursor, N-acetylcysteine (NAC), also showed reduced mortality and pericardial edema; however, fin malformations were not reduced. Conversely, co-exposure to the GSH synthesis inhibitors, buthionine sulfoximine (BSO) and diethyl maleate (DEM), increased the sensitivity of zebrafish to C-60 exposure. Co-exposure of C-60 or its hydroxylated derivative, C-60(OH)(24), with H2O2 resulted in increased mortality along the concentration gradient of H2O2 for both materials. Microarrays were used to examine the effects of C-60 on the global gene expression at two time points, 36 and 48 h post fertilization (hpf). At both life stages there were alterations in the expression of several key stress response genes including glutathione-S-transferase, glutamate cysteine ligase, ferritin, a-tocopherol transport protein and heat shock protein 70. These results support the hypothesis that C-60 induces oxidative stress in this model system. (C) 2008 Elsevier Inc. All rights reserved.