Co-exposure of the organic nanomaterial fullerene C60 with benzo[a]pyrene in Danio rerio (zebrafish) hepatocytes: Evidence of toxicological interactions

Compounds from the nanotechnology industry, such as carbon-based nanomaterials, are strong candidates to contaminate aquatic environments because their production and disposal have exponentially grown in a few years. Previous evidence shows that fullerene C60, a carbon nanomaterial, can facilitate the intake of metals or PAHs both in vivo and in vitro, potentially amplifying the deleterious effects of these toxicants in organisms. The present work aimed to investigate the effects of fullerene C60 in a Danio rerio (zebrafish) hepatocyte cell lineage exposed to benzo[a]pyrene (BaP) in terms of cell viability, oxidative stress parameters and BaP intracellular accumulation. Additionally, a computational docking was performed to investigate the interaction of the fullerene C60 molecule with the detoxificatory and antioxidant enzyme πGST. Fullerene C60 provoked a significant (p 0.05) alter the enzyme activity when added to GST purified extracts from the zebrafish hepatocyte cells. These results show that fullerene C60 can increase the intake of BaP into the cells, decreasing cell viability and impairing the detoxificatory response by phase II enzymes, such as GST, and this latter effect should be occurring at the transcriptional level.Fil: Ribas Ferreira, Josencler L.. Universidade Federal do Rio Grande do Sul; BrasilFil: Lonné, María Noelia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: França, Thiago A.. Universidade Federal do Rio Grande do Sul; BrasilFil: Maximilla, Naiana R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Lugokenski, Thiago H.. Universidade Federal de Santa Maria. Departamento de Química; BrasilFil: Costa, Patrícia G.. Universidade Federal do Rio Grande do Sul; BrasilFil: Fillmann, Gilberto. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Félix A.. Universidade Federal de Santa Maria. Departamento de Química; BrasilFil: de la Torre, Fernando Roman. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas; ArgentinaFil: Monserrat, José María. Universidade Federal do Rio Grande do Sul; Brasil. Instituto Nacional de Ciência e Tecnologia de Nanomateriais de Carbono; Brasi

Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster

The compounds 4-vinylcyclohexene 1,2-monoepoxide (VCM) and 4-Vinylcyclohexene diepoxide (VCD) are the two downstream metabolites of 4-vinylcyclohexene (VCH), an ovotoxic agent in mammals. In addition, VCM and VCD may be found as by-products of VCH oxidation in the environment. Recently, we reported the involvement of oxidative stress in the toxicity of VCH in Drosophila melanogaster. However, it was not possible to determine the individual contributions of VCM and VCD in VCH toxicity. Hence, we investigated the toxicity of VCM and VCD (10–1000 µM) in flies after 5 days of exposure via the diet. Our results indicated impairments in climbing behaviour and disruptions in antioxidant balance and redox status evidenced by an increase in DCFH oxidation, decreases in total thiol content and glutathione-S-transferase (GST) activity in the flies exposed to VCM and VCD (p<0.05). These effects were accompanied by disruptions in the transcription of the genes encoding the proteins superoxide dismutase (SOD1), kelch-like erythroid-derived cap-n-collar (CNC) homology (ECH)-associated protein 1 (Keap-1), mitogen activated protein kinase 2 (MAPK-2), catalase, Cyp18a1, JAFRAC 1 (thioredoxin peroxidase 1) and thioredoxin reductase 1 (TrxR-1) (p<0.05). VCM and VCD inhibited acetylcholinesterase (AChE) and delta aminolevulinic acid dehydratase (δ-ALA D) activities in the flies (p<0.05). Indeed, here, we demonstrated that different target enzymes and genes were modified by the electrophiles VCM and VCD in the flies. Thus, D. melanogaster has provided further lessons on the toxicity of VCM and VCD which suggest that the reported toxicity of VCH may be mediated by its transformation to VCM and VCD. Keywords: 4-Vinylcyclohexene 1,2-monoepoxide, 4-Vinylcyclohexene diepoxide, Reactive oxygen and nitrogen species, Changes in mRNA levels, Disruption of antioxidant homoeostasi