Kidney injury contributes to edema of zebrafish larvae caused by quantum dots.

Edema represents a notable outcome in fishes exposed to aquatic pollutants, yet the underlying etiology remains inadequately understood. This investigation delves into the etiological factors of edema formation in 7 days post fertilization (dpf) zebrafish larvae following their exposure to InP/ZnS quantum dots (QDs), which was chosen as a prototypical edema inducer. Given the fundamental role of the kidney in osmoregulation, we used transgenic zebrafish lines featuring fluorescent protein labeling of the glomerulus, renal tubule, and blood vessels, in conjunction with histopathological scrutiny. We identified the pronounced morphological and structural aberrations within the pronephros. By means of tissue mass spectrometry imaging and hyperspectral microscopy, we discerned the accumulation of InP/ZnS QDs in the pronephros. Moreover, InP/ZnS QDs impeded the renal clearance capacity of the pronephros, as substantiated by diminished uptake of FITC-dextran. InP/ZnS QDs also disturbed the expression levels of marker genes associated with kidney development and osmoregulatory function at the earlier time points, which preceded the onset of edema. These results suggest that impaired fluid clearance most likely resulting from pronephros injury contributes to the emergence of zebrafish edema. Briefly, our study provides a perspective: the kidney developmental injury induced by exogenous substances may regulate edema in a zebrafish model.

Exposure to echimidine impairs the heart development and function of zebrafish larvae.

Pyrrolizidine alkaloids (PAs) are a class of phytotoxins that are widely distributed and can be consumed by humans through their daily diets. Echimidine is one of the most abundant PAs, but its safety, particularly its effects on development, is not fully understood. In this study, we used a zebrafish model to assess the developmental toxicity of echimidine. Zebrafish embryos were exposed to echimidine at concentrations of 0.02, 0.2, and 2 mg/L for 96 h. Our study revealed that embryonic exposure to echimidine led to developmental toxicity, characterized by delayed hatching and reduced body length. Additionally, echimidine exposure had a notable impact on heart development in larvae, causing tachycardia and reducing stroke volume (SV)and cardiac output (CO). Upon exposing the transgenic zebrafish strain Tg(cmlc2:EGFP) to echimidine, we observed atrial dilation and thinning of the atrial wall in developing embryos. Moreover, our findings indicated abnormal expression of genes associated with cardiac development (including gata4, tbx5, nkx2.5 and myh6) and genes involved in calcium signaling pathways (such as cacna1aa, cacna1sa, ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a1, slc8a3 and slc8a4a). In summary, our findings demonstrate that echimidine may impair cardiac development and function in zebrafish larvae by disrupting calcium transport, leading to developmental toxicity. These findings provide insights regarding the safety of products containing PAs in food and medicine.

The valence state of iron-based nanomaterials determines the ferroptosis potential in a zebrafish model.

Many nanomaterials containing different valences of iron have been designed for applications in biomedicine, energy, catalyzers, nanoenzymes, and so on. However, the toxic effects of the valence state of iron in iron-based nanomaterials are still unclear. Here, three different-valence iron-based nanomaterials (nFe@Fe3O4, nFe3O4 and nFe2O3) were synthesized and exposed to zebrafish embryos and mammalian cardiomyocytes. All of them induced ferroptosis along with an increase in valence through iron overload and the Fenton reaction. Specifically, we exposed Tg (cmlc2:EGFP) zebrafish to the three iron-based nanomaterials and found that nFe@Fe3O4 treatments led to enlarged ventricles, while nFe3O4 and nFe2O3 increased atrial size, which was consistent with the results from hematoxylin-eosin staining and in situ hybridization. Moreover, we used ferroptosis inhibitors (ferrostatin-1 or deferoxamine) to treat zebrafish along with nanoparticles exposure and found that the cardiac developmental defects caused by nFe3O4 and nFe2O3, but not nFe@Fe3O4, could be completely rescued by ferroptosis inhibitors. We further found that nFe@Fe3O4, rather than nFe3O4 and nFe2O3, reduced the dissolved oxygen in the medium, which resulted in hypoxia and acceleration of heart tube formation and ventricular enlargement, and both were fully rescued by oxygen donors combined with ferroptosis inhibitors. Consistently, these findings were also observed in mammalian cardiomyocytes. In summary, our study demonstrates that the valence state of iron-based nanomaterials determines the ferroptosis potential. Our study also clarifies that high-valence iron-based nanomaterials induce an enlarged atrium via ferroptosis, while low-valence ones increase the ventricular size through both hypoxia and ferroptosis, which is helpful to understand the potential adverse effects of different valences of iron-based nanomaterials on environmental health and assure the responsible and sustainable development of nanotechnology.

Sacran polysaccharide improves atopic dermatitis through inhibiting Th2 type immune response.

AIMS: This study was aimed to explore whether sacran polysaccharide has a therapeutic effect on atopic dermatitis (AD) and its possible mechanisms. MATERIALS AND METHODS: 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice were treated with 0.2% Sacran, 0.5% Sacran and 0.1% tacrolimus. Through scoring dermatitis severity, measuring ear thickness, cracking behavior, open field test, we evaluated the therapeutic effect of Sacran on DNCB-induced AD mice. CD4+ T cells and CD8+ T cells were evaluated by flow cytometry. The relative expression of Ifng and Il4 were measured by real-time quantitative PCR. KEY FINDINGS: Sacran could relieved the symptoms of DNCB-induced AD mice, such as AD score, ear thickness, and IgE release. Sacran may alleviate dermatitis by inhibiting Th2 activation and reducing IgE release. SIGNIFICANCE: Our research further proved that polysaccharide Sacran has anti-dermatitis effects, and also clarified its mechanism of alleviating dermatitis by inhibiting the activation of Th2 cells and reducing the release of IgE, which provides a theoretical basis for the future clinical transformation of polysaccharide Sacran.