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首页> 外文期刊>International Journal of Nanomedicine >Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells
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Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells

机译：金刚石，氧化石墨烯和石墨的纳米结构抑制CYP1A2，CYP2D6和CYP3A4酶并下调肝细胞中的基因

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Introduction and objective: Currently, carbon nanostructures are vastly explored materials with potential for future employment in biomedicine. The possibility of employment of diamond nanoparticles (DN), graphene oxide (GO) or graphite nanoparticles (GN) for in?vivo applications raises a question of their safety. Even though they do not induce a direct toxic effect, due to their unique properties, they can still interact with molecular pathways. The objective of this study was to assess if DN, GO and GN affect three isoforms of cytochrome P450 (CYP) enzymes, namely, CYP1A2, CYP2D6 and CYP3A4, expressed in the liver. Methods: Dose-dependent effect of the DN, GO and GN nanostructures on the catalytic activity of CYPs was examined using microsome-based model. Cytotoxicity of DN, GO and GN, as well as the influence of the nanostructures on mRNA expression of CYP genes and CYP-associated receptor genes were studied in vitro using HepG2 and HepaRG cell lines. Results: All three nanostructures interacted with the CYP enzymes and inhibited their catalytic activity in microsomal-based models. CYP gene expression at the mRNA level was also downregulated in HepG2 and HepaRG cell lines. Among the three nanostructures, GO showed the most significant influence on the enzymes, while DN was the most inert. Conclusion: Our findings revealed that DN, GO and GN might interfere with xenobiotic and drug metabolism in the liver by interactions with CYP isoenzymes responsible for the process. Such results should be considered if DN, GO and GN are used in medical applications.
机译：引言和目的：目前，碳纳米结构是被广泛研究的材料，具有未来在生物医学中应用的潜力。在体内应用中采用金刚石纳米颗粒（DN），氧化石墨烯（GO）或石墨纳米颗粒（GN）的可能性提出了其安全性的问题。尽管它们不具有直接的毒性作用，但由于其独特的性能，它们仍然可以与分子途径相互作用。这项研究的目的是评估DN，GO和GN是否影响肝脏中表达的三种细胞色素P450（CYP）酶同工型，即CYP1A2，CYP2D6和CYP3A4。方法：使用基于微粒体的模型，研究了DN，GO和GN纳米结构的剂量依赖性效应对CYPs催化活性的影响。使用HepG2和HepaRG细胞系体外研究了DN，GO和GN的细胞毒性，以及纳米结构对CYP基因和CYP相关受体基因mRNA表达的影响。结果：在基于微粒体的模型中，所有三个纳米结构均与CYP酶相互作用并抑制其催化活性。 CYP基因在mRNA水平的表达在HepG2和HepaRG细胞系中也下调。在这三个纳米结构中，GO对酶的影响最大，而DN最惰性。结论：我们的研究结果表明，DN，GO和GN可能通过与负责该过程的CYP同工酶相互作用而干扰肝脏中的异种生物和药物代谢。如果在医疗应用中使用DN，GO和GN，则应考虑此类结果。

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