title: Fullerene C60 exposure elicits an oxidative stress response in embryonic zebrafish.
abstract: Due to its unique physicochemical and optical properties, C60 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 C60, the effects of light and chemical supplementation and depletion of glutathione (GSH) on C60-induced toxicity were evaluated. Embryonic zebrafish were used as a model organism to examine the potential of C60 to elicit oxidative stress responses. Reduced light during C60 exposure significantly decreased mortality and the incidence of fin malformations and pericardial edema at 200 and 300 ppb C60. 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 C60 exposure. Co-exposure of C60 or its hydroxylated derivative, C60(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 C60 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, alpha-tocopherol transport protein and heat shock protein 70. These results support the hypothesis that C60 induces oxidative stress in this model system.
authors.affiliation: Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, 1007 ALS, Oregon State University, Corvallis, OR 97331-7301, USA.
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Usenko
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Harper
authors.forename: Robert L
authors.initials: RL
authors.lastname: Tanguay
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005293:Ferritins / Q000187:drug effects / Q000378:metabolism; D037741:Fullerenes / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008027:Light; D008298:Maleates / Q000494:pharmacology; D046228:Microarray Analysis; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D010490:Pericardial Effusion / Q000139:chemically induced; D013997:Time Factors; D015027:Zebrafish
chemical_list: D002352:Carrier Proteins; D037741:Fullerenes; D018840:HSP70 Heat-Shock Proteins; D008298:Maleates; C017763:alpha-tocopherol transfer protein; D019328:Buthionine Sulfoximine; D005293:Ferritins; D006861:Hydrogen Peroxide; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; C014476:diethyl maleate; C069837:fullerene C60; D000111:Acetylcysteine