The combined effects of graphene oxide and bisphenol A on oxidative damage in early development of zebrafish

Abstract

Bisphenol A (BPA) is widely present in natural surface water, and was found to be at the high level of μg/L in the surface water around a BPA manufacturing plant. Mass production and application make BPA ubiquitous in the environment, biota and humans. As a two-dimensional carbon based nanomaterial, graphene oxide (GO) is used in many fields, and there is a great potential for GO to discharge to aquatic environment via various pathways. Thus GO has the potential to interact with organic pollutants, such as BPA, copresent in water system. GO could adsorb organic pollutants in water, and adhere on the surface of organisms, displaying different effects on the behaviors and toxicities of organic pollutants in organisms at different developmental stages. But the intrinsic mechanisms for the different effects remain unclear. To fill this gap, zebrafish ( Danio rerio ) was selected as a vertebrate model to investigate the toxicities of a variety of pollutants and nanomaterials in this study. Embryogenesis is an important growth phase in the zebrafish life cycle. Pollutants can induce excessive reactive oxygen species (ROS) and generate a large number of oxidative intermediate products by destroying the balance between oxidation and antioxidation, thus causing oxidative damage. Superoxide dismutase (SOD) can catalyze the oxidation of superoxide anion (O2−) to O2 and H2O, in an attempt to maintain ROS at a physiological level and protect the body from damage. Catalase (CAT) exists primarily within peroxisomes and removes the H2O2 generated by the long-chain fatty acid β-oxidation pathway. Excessive ROS can attack the polyunsaturated fatty acids in the biomembrane system, resulting in lipid peroxidation. Malondialdehyde (MDA) is the product of irreversible lipid peroxidation, and the change of MDA can reflect the level and damage degree of lipid peroxidation in organisms. Glutathione (GSH), as an important non-enzymatic antioxidant in organism, can be induced and effectively scavenged by external stimulation to regulate oxidative stress. Toxic effects occur in organisms when GSH is gradually reduced. This study focused on the joint effects of GO and BPA on the oxidative responses in zebrafish at early development stage. Zebrafish embryos were individually exposed to BPA (0, 50, 500 µg/L), GO (0, 0.1, 1 mg/L), BPA+GO (50 µg/L+ 0.1 mg/L, 500 µg/L+ 0.1 mg/L, and 50 µg/L +1 mg/L, 500 µg/L +1 mg/L) solutions for 7 d. The levels of SOD, MDA, GSH, CAT, and ROS in the exposed zebrafish larvae were determined. The results indicated that BPA displayed strong oxidative damage effects on zebrafish larvae. However, the presence of GO distinctly alleviated the various indicators of oxidative damages caused by BPA. Based on analyses using the Bliss independence model, GO and BPA exhibited antagonistic effects on the oxidative damage of zebrafish in the early development stage, which indicated that GO could reduce the oxidative damage toxicities of BPA on zebrafish embryos under the experimental conditions. These could be due to the formation of a GO layer on the zebrafish embryos, which depressed the absorption of BPA by zebrafish, leading to reduced BPA accumulation in zebrafish in early developmental stage.