Melissa Dibbernn Ganzerla , Nathalia de Carvalho Indolfo , Larissa Cleres Moreira Oliveira , Tabata Renee Doratioto , Thayná Mendonça Avelino , Rafael Junior de Azevedo , Larissa Bueno Tofani , Maiara Ferreira Terra , Giovanna Blazutti Elias , Irene Layane de Sousa , Marcos Rodrigo Alborguetti , Silvana Aparecida Rocco , Kelen Fabiola Arroteia , Ana Carolina Migliorini Figueira
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引用次数: 0
摘要
由于人们对双酚 A(BPA)及其替代品双酚 S(BPS)可能对健康产生的不利影响感到担忧,因此对其进行了创新性探索。在一些地区,双酚 S 取代了双酚 A,以避免有毒影响,但这方面的研究仍然不足。除此之外,器官芯片技术作为一种变革性的解决方案出现在药物发现和化学毒性测试领域,通过整合不同的组织和动态细胞环境提高预测器官功能的精确度,从而减少对动物模型的依赖,最大限度地降低成本并符合道德标准。在这里,我们采用了一种带有皮肤、肠道和肝脏培养物的三器官芯片微流控装置,通过局部和口服给药来评估双酚 A 和双酚 S 的影响。我们的评估重点是与致癌性、全身毒性和内分泌干扰有关的基因标记。双酚 A 表现出预期的吸收特征,导致肝脏损伤和相关途径的基因调控。作为一种更安全的替代品,双酚 A 会对基因表达产生不利影响,特别是在局部吸收时,吸收模式截然不同。我们的研究结果强调了解决双酚 A 和双酚 S 毒性问题的紧迫性,突出了器官芯片技术在了解相关健康风险方面的关键作用。这项研究推动器官芯片方法成为安全药物开发和疾病治疗的重要工具,为传统动物试验提供了一种新的肝脏毒性筛选替代方法。这有助于进一步了解这些化合物的生物效应,从而改进对人类健康的安全评估。
Unveiling the intricacies of BPA and BPS: comprehensive insights into its toxic effects using a cutting-edge microphysiological system
Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function.
Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.
期刊介绍:
Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.