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五种金属纳米颗粒对小鼠肝脏中主要药物代谢酶基因表达的影响及其与炎症的相关性。

The influence of five metallic nanoparticles on the expression of major drug-metabolizing enzyme genes with correlation of inflammation in mouse livers.

机构信息

Department of Pharmaceutical Science, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Jordan.

Department of Biology, College of Science, King Khalid University, Saudi Arabia.

出版信息

Environ Toxicol Pharmacol. 2020 Nov;80:103449. doi: 10.1016/j.etap.2020.103449. Epub 2020 Jun 25.

Abstract

Metallic nanoparticles (NPs) are widely used in medical preparations. The present study aims to find out the influence of widely used five metallic NPs on the expression of major hepatic drug-metabolizing enzyme (DME) genes. Six groups of BALB/C mice, 7 mice each, were exposed to: Gold NPs, silver NPs, copper oxide NPs, silicon dioxide NPs and zinc oxide NPs, for 21 days. Liver biopsies from all mice were subjected to mouse cyp3a11, cyp2c29, ugt2b1 and interleukin-6 (il6) gene expression quantification using real-time polymerase chain reaction, in addition to inflammatory cell infiltration examination. All tested NPs caused a sharp and significant (ANOVA, p value <0.05) downregulation in the expression of DME genes, with the highest influence was observed in mice exposed to copper oxide NPs. Additionally, all NPs induced hepatic inflammation and upregulated the expression of il6 gene, which were inversely correlated with the expression of DMEs. It is concluded that all tested NPs downregulated the expression of DME genes, with the highest influence exhibited by copper oxide NPs, in correlation with inflammation and il6 gene induction in the liver. Further studies are needed to find out the effect of anti-inflammatory compounds against the alterations induced by metallic NPs exposure on hepatic DMEs.

摘要

金属纳米粒子(NPs)广泛应用于医疗制剂中。本研究旨在探讨广泛使用的五种金属 NPs 对主要肝药物代谢酶(DME)基因表达的影响。将 6 组 BALB/C 小鼠(每组 7 只)分别暴露于金 NPs、银 NPs、氧化铜 NPs、二氧化硅 NPs 和氧化锌 NPs 中 21 天。通过实时聚合酶链反应,对所有小鼠的肝活检进行小鼠 CYP3A11、CYP2C29、UGT2B1 和白细胞介素 6(IL6)基因表达定量检测,并检查炎症细胞浸润情况。所有测试的 NPs 均导致 DME 基因表达明显下调(方差分析,p 值<0.05),其中氧化铜 NPs 的影响最大。此外,所有 NPs 均诱导肝脏炎症和 IL6 基因表达上调,这与 DMEs 的表达呈负相关。综上所述,所有测试的 NPs 均下调 DME 基因的表达,其中氧化铜 NPs 的影响最大,与肝脏炎症和 IL6 基因诱导有关。需要进一步研究以确定抗炎化合物对金属 NPs 暴露引起的肝 DMEs 改变的影响。

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