The developmental toxicity of nanostructured materials, as well as their impact on the biological barriers, represents a crucial aspect to be assessed in a nanosafety policy framework. Nanosized metal oxides have been demonstrated to affect Xenopus laevis embryonic development, with nZnO specifically targeting the digestive system. To study the mechanisms of the nZnO-induced intestinal lesions, we tested two different nominally sized ZnO nanoparticles (NPs) at effective concentrations. Advanced microscopy techniques and molecular marker analyses were applied in order to describe the NP-epithelial cell interactions and the mechanisms driving NP toxicity and translocation through the intestinal barrier. We attributed the toxicity to NP-induced cell oxidative damage, the small-sized NPs being the more effective. This outcome is sustained by a marked increase in anti-oxidant genes' expression and high lipid peroxidation level in the enterocytes, where disarrangement of the cytoskeleton and cell junctions' integrity were evidenced. These events led to diffuse necrotic changes in the intestinal barrier, and trans- and paracellular NP permeation through the mucosa. The uptake routes, leading NPs to cross the intestinal barrier and reach secondary target tissues, have been documented. nZnOs embryotoxicity was confirmed to be crucially mediated by the NPs' reactivity rather than their dissolved ions. The ZnO NPs' ability to overwhelm the intestinal barrier must be taken into high consideration for a future design of safer ZnO NPs.

中文翻译：

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Xenopus laevis中氧化锌纳米颗粒通过胃肠道屏障的证据和吸收途径。

纳米结构材料的发育毒性及其对生物屏障的影响，是需要在纳米安全政策框架中评估的关键方面。事实证明，纳米金属氧化物会影响非洲爪蟾的胚胎发育，其中nZnO专门针对消化系统。为了研究nZnO诱导的肠道损伤的机制，我们在有效浓度下测试了两种不同的名义上大小的ZnO纳米颗粒（NPs）。为了描述NP-上皮细胞相互作用以及驱动NP毒性和通过肠屏障转运的机制，应用了先进的显微镜技术和分子标记分析。我们将毒性归因于NP诱导的细胞氧化损伤，小尺寸的NPs更有效。肠细胞中抗氧化基因表达的明显增加和脂质过氧化水平的显着提高，从而维持了这一结果，其中证明了细胞骨架的紊乱和细胞接头的完整性。这些事件导致肠屏障弥漫性坏死改变，以及跨粘膜的跨细胞和旁细胞的NP渗透。已经记录了导致NPs穿过肠屏障并到达次级靶组织的吸收途径。证实nZnOs的胚胎毒性是由NPs的反应性而不是其溶解的离子决定性的介导的。为了将来设计更安全的ZnO NP，必须高度考虑ZnO NP克服肠道屏障的能力。那里的细胞骨架和细胞连接的完整性紊乱被证明。这些事件导致肠屏障弥漫性坏死改变，以及跨粘膜的跨细胞和旁细胞的NP渗透。已经记录了导致NPs穿过肠屏障并到达次级靶组织的吸收途径。证实nZnOs的胚胎毒性是由NPs的反应性而不是其溶解的离子决定性的介导的。为了将来设计更安全的ZnO NP，必须高度考虑ZnO NP克服肠道屏障的能力。那里的细胞骨架和细胞连接的完整性紊乱被证明。这些事件导致肠屏障弥漫性坏死改变，以及跨粘膜的跨细胞和旁细胞的NP渗透。已经记录了导致NPs穿过肠屏障并到达次级靶组织的吸收途径。证实nZnOs的胚胎毒性是由NPs的反应性而不是其溶解的离子决定性的介导的。为了将来设计更安全的ZnO NP，必须高度考虑ZnO NP克服肠道屏障的能力。导致NPs穿过肠屏障并到达次要靶组织的文献已被记录。证实nZnOs的胚胎毒性是由NPs的反应性而不是其溶解的离子决定性的介导的。为了将来设计更安全的ZnO NP，必须高度考虑ZnO NP克服肠道屏障的能力。导致NPs穿过肠屏障并到达次要靶组织的文献已被记录。证实nZnOs的胚胎毒性是由NPs的反应性而不是其溶解的离子决定性的介导的。为了将来设计更安全的ZnO NP，必须高度考虑ZnO NP克服肠道屏障的能力。