Application of organoid technology in the human health risk assessment of microplastics: A review of progresses and challenges.

Microplastic (MP) pollution has become a global environmental issue, and increasing concern has been raised about its impact on human health. Current studies on the toxic effects and mechanisms of MPs have mostly been conducted in animal models or in vitro cell cultures, which have limitations regarding inter-species differences or stimulation of cellular functions. Organoid technology derived from human pluripotent or adult stem cells has broader prospects for predicting the potential health risks of MPs to humans. Herein, we reviewed the current application advancements and opportunities for different organoids, including brain, retinal, intestinal, liver, and lung organoids, to assess the human health risks of MPs. Organoid techniques accurately simulate the complex processes of MPs and reflect phenotypes related to diseases caused by MPs such as liver fibrosis, neurodegeneration, impaired intestinal barrier and cardiac hypertrophy. Future perspectives were also proposed for technological innovation in human risk assessment of MPs using organoids, including extending the lifespan of organoids to assess the chronic toxicity of MPs, and reconstructing multi-organ interactions to explore their potential in studying the microbiome-gut-brainaxis effect of MPs.

Plastic food? Energy compensation of zebrafish (Danio rerio) after long-term exposure to polylactic acid biomicroplastics.

The extensive use of bio-based plastics has led to their widespread distribution in the environment. However, their long-term ecological impact on aquatic animals is not well understood. In this study, adult zebrafish (Danio rerio) were exposed to 1000 items·L-1 of either polylactic acid (PLA) or polyethylene terephthalate (PET) microplastics (MPs), for 90 days. PLA is a typical bio-based plastic, while PET is a typical petroleum-derived plastic. The abundances of PLA and PET MPs in fish intestines were 981 ± 66 and 671 ± 151 items per fish, respectively, indicating a greater amount of PLA MP residues than PET MPs. However, the inhibitory effect of PET on fish weight was 1.8 times higher than that of PLA, suggesting energy compensation in PLA-treated zebrafish. Proliferation of Lactobacillus was observed in the fish intestines of the PLA group, indicating increased utilization capacity of intestinal flora for lactic acid production during PLA degradation. Metabolomics showed that the tricarboxylic acid pathway was up-regulated in the PLA group compared with that in the PET group, providing evidence of energy compensation. However, more ingested PLA MPs caused more significant histological damage to fish intestines than PET MPs. Therefore, the ecological risks of bio-based plastics still require attention.

Ecological risk assessment for typical organophosphorus pesticides in surface water of China based on a species sensitivity distribution model.

The ecological risks posed by widespread organophosphorus pesticide (OPs) pollution in the surface waters of China remain unclear. In this study, species sensitivity distribution (SSD) parametric statistical approaches were coupled with fully acute and chronic toxicity data to fit the sensitivity distributions of different aquatic species to five typical OPs: dimethoate, malathion, parathion-methyl, trichlorfon, and dichlorvos. Crustaceans exhibit the highest sensitivity to OPs, whereas algae are the least sensitive. The acute hazardous concentrations that affected 5 % of the species (HC5) were 0.112, 0.001, 0.001, 0.001, and 0.001 mg/L for dimethoate, malathion, parathion-methyl, trichlorfon, and dichlorvos, respectively, whereas their chronic HC5 values were 0.004, 0.004, 0.053, 0.001, and 0.0005 mg/L, respectively. Hence, dichlorvos is highly toxic and poses greater risk to non-target aquatic species. The evaluation data revealed varying geographical distribution characteristics of the ecological risks from OPs in 15 freshwater aquatic systems across different regions of China. Dichlorvos posed the highest risk in the basins of Zhejiang and Guangdong Provinces, with the highest chronic Risk Quotient (RQ) and Hazard Index (HI) at 9.34 and 9.92, respectively. This is much higher than what was collected and evaluated for foreign rivers (the highest chronic RQ and HI in foreign rivers were 1.65 and 2.24, respectively). Thus, dichlorvos in the surface waters of China poses a substantial ecological risk to aquatic organisms, and may endanger human health.

Nanoplastics induce neuroexcitatory symptoms in zebrafish (Danio rerio) larvae through a manner contrary to Parkinsonian's way in proteomics.

Although nanoplastics (NPs) can penetrate the blood-brain barrier and accumulate in the brain, the neurotoxicity of these particles and the mechanisms associated with their unique physio-chemical properties have yet to be sufficiently ascertained. In this study, we assessed the neuroexcitatory symptoms of zebrafish (Danio rerio) larvae treated with polystyrene (PS) NPs based on an examination of locomotory behaviour, dopamine levels, and acetylcholinesterase activity. We found that PS NPs caused oxidative stress and inhibited atoh1a expression in the cerebellum of Tg(atoh1a:dTomato) transgenic zebrafish larvae, thereby indicating damage to the central nervous system. In contrast to the Parkinson's disease (PD) like effects induced by most types of nanoparticles, such as graphene oxide, we established that PS NPs influenced the neuronal proteomic profiles of zebrafish larvae in a manner contrary to the molecular pathways characteristic of PD-like effects, which could be explained by the molecular dynamic simulation. Unlike graphene oxide nanoparticles that promote significant change in the internal structure of neuroproteins, the complex macromolecular polymers of PS NPs promoted the coalescence and increased expression of neuroproteins, thereby plausibly contributing to the neuroexcitatory symptoms observed in treated zebrafish larvae. Consequently, compared with traditional nanoparticles, we believe that the unique physio-chemical properties of NPs could be a potential factor contributing to their toxicity.

Elevated temperature decreases cardiovascular toxicity of nanoplastics but adds to their lethality: A case study during zebrafish (Danio rerio) development.

To highlight the key role of global warming on the toxicity of contaminants, the cardiovascular toxicity of nanoparticles (NPs) was estimated in developing zebrafish (Danio rerio) at different exposure temperatures, and the toxicity mechanisms were explored via multi-omic analyses. Polystyrene NPs (50 nm) at 0.1 mg·L-1 entered zebrafish embryos at 24 h post-fertilization and caused cardiovascular toxicity in the developing zebrafish at 27 ℃. This was explained by the down-regulation of the branched-chain amino acid and insulin signaling pathways owing to induced oxidative stress. Elevated exposure temperatures promoted the accumulation of NPs in developing zebrafish, increased the levels of oxidative stress and enhanced the oxidative phosphorylation rate in mitochondria, thus resulting in an additive effect on the mortality of zebrafish larvae. Notably, elevated exposure temperatures reduced the cardiovascular toxicity of NPs, as the effective concentration of NPs for inhibiting embryonic heartbeat rate increased from 0.1 mg·L-1 at 27 ℃ to 1.0 mg·L-1 at 30 ℃. Experiments of transgenic zebrafish Tg(myl7:GFP) and multi-omic analyses revealed that elevated temperatures enhanced the myocardial contractility of larvae, thus reducing the cardiovascular toxicity of NPs. However, the health risks of enhanced myocardial contraction caused by NP exposure at elevated temperatures requires further consideration.