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Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
Published on: June 5, 2020
Microplastics in motion: Genotoxic and redox imbalance impacts of systemic exposure in a murine model
Wesley Rodrigues Soares1, Thiarlen Marinho da Luz2, Raíssa de Oliveira Ferreira3
1Post-Graduation Program in Conservation of Cerrado Natural Resources, Goiano Federal Institute, Urutaí, GO 75790-000, Brazil; Laboratory of Toxicology Applied to the Environment, Goiano Federal Institute - Urutaí Campus. Rodovia Geraldo Silva Nascimento, 2,5 km, Zona Rural, Urutaí, GO 75790-000, Brazil.
Abstract:
The increasing dissemination of microplastics (MPs) in the environment and their potential adverse effects on human and animal health have raised significant concerns in the scientific community. In this context, we aimed to investigate the toxicity induced by polyethylene (PE) MPs in the blood of Swiss mice (Mus musculus), focusing on biomarkers of oxidative and nitrosative stress and genotoxicity. Thirty mice were distributed across three experimental groups: two groups intravenously inoculated with polyethylene MPs at target systemic blood concentrations of 7.1 µg/mL and 355 µg/mL, respectively, and a non-exposed control group. After five days of intravenous (single) exposure to MPs, analyses revealed particles in the blood, liver, and kidneys, indicating selective retention in these tissues. While the Comet assay demonstrated increased DNA damage in peripheral blood, corroborating the genotoxicity of MPs, biochemical analyses revealed a complex response that depended on the organ and the biomarker evaluated. In the liver, we observed a significant reduction in the oxidative stress index, a metric that integrates pro-oxidant parameters (ROS and MDA) in relation to the endogenous antioxidant activities of SOD and CAT. At the same time, in the kidneys, there was an increase in the ratio between SOD and CAT activity. In both organs, increased nitrite production suggests the induction of marked nitrosative stress. On the other hand, in the liver, MDA levels surprisingly decreased, suggesting that MPs may interfere with lipid peroxidation pathways or promote the diversion of ROS toward NO-mediated peroxynitrite formation, reducing classical lipid oxidative damage. Principal Component Analysis (PCA) and cluster analysis provided an exploratory and integrative overview of the dataset, revealing distinct biochemical patterns between the control and MP-exposed groups, with higher MP concentrations associated with more pronounced oxidative and genotoxic responses. Thus, we conclude that exposure to MPs can cause significant cellular damage, reinforcing the need for further research to understand the risks associated with MP contamination and to develop effective mitigation strategies.

