Simple SummaryRecent reports focusing on the extent of plastic pollution have shown that petroleum-based products can currently be found in most marine species, which is a consequence of the immense production and use of plastics. The severe contamination of plastic nano-/microparticles (NPs/MPs) mainly results in immediate negative outcomes, such as organic impairments and tissue damage, as well as long-termed negative effects, such as developmental retardation and defects, chronic inflammation, oxidative stress (OS), metabolic imbalance, mutagenesis, and teratogenesis. We aimed to correlate the possible toxic effects of plastic NPs/MPs in zebrafish models, by focusing on OS and developmental processes, and the size, shape, and doses of the NPs/MPs. We found that plastic NPs/MPs toxic effects could be observed during the entire developmental span of zebrafish in close correlation with OS-related changes. The decreased antioxidant enzymatic defense due to plastic NPs/MPs exposure and accumulation suggests important neurodevelopmental negative outcomes (cognitive abnormalities, neurodevelopmental retardation, and behavioral impairments) and neuronal effects, such as impaired digestive physiology.AbstractRecent reports focusing on the extent of plastic pollution have shown that many types of fibers and polymers can now be found in most marine species. The severe contamination of plastic nano-/microparticles (NPs/MPs) mainly results in immediate negative outcomes, such as organic impairments and tissue damage, as well as long-termed negative effects, such as developmental retardation and defects, chronic inflammation, oxidative stress (OS), metabolic imbalance, mutagenesis, and teratogenesis. Oxidative responses are currently considered the first line molecular signal to potential toxic stimuli exposure, as the oxidative balance in electron exchange and reactive oxygen species signaling provides efficient harmful stimuli processing. Abnormal signaling or dysregulated ROS metabolism—OS—could be an important source of cellular toxicity, the source of a vicious cycle of environmental and oxidative signaling-derived toxicity. As chemical environmental pollutants, plastic NPs/MPs can also be a cause of such toxicity. Thus, we aimed to correlate the possible toxic effects of plastic NPs/MPs in zebrafish models, by focusing on OS and developmental processes. We found that plastic NPs/MPs toxic effects could be observed during the entire developmental span of zebrafish in close correlation with OS-related changes. Excessive ROS production and decreased antioxidant enzymatic defense due to plastic NPs/MPs exposure and accumulation were frequently associated with acetylcholinesterase activity inhibition, suggesting important neurodevelopmental negative outcomes (cognitive abnormalities, neurodevelopmental retardation, behavioral impairments) and extraneuronal effects, such as impaired digestive physiology.