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The influence of five metallic nanoparticles on the expression of major drug-metabolizing enzyme genes with correlation of inflammation in mouse livers.
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-06-25 , DOI: 10.1016/j.etap.2020.103449
Yazun Jarrar 1 , Amin Al-Doaiss 2 , Mohammad Alfaifi 2 , Ali Shati 2 , Mohammed Al-Kahtani 2 , Bashir Jarrar 3
Affiliation  

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.



中文翻译:

五个金属纳米粒子对主要药物代谢酶基因表达与小鼠肝脏炎症相关性的影响。

金属纳米颗粒(NPs)广泛用于医疗制剂。本研究旨在发现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。将六组BALB / C小鼠(每组7只)暴露于:金NP,银NP,氧化铜NP,二氧化硅NP和氧化锌NP,持续21天。除炎症细胞浸润检查外,还使用实时聚合酶链反应对所有小鼠的肝活检样本进行了cyp3a11cyp2c29ugt2b1白细胞介素6(il6)基因表达定量。所有测试的NP均引起尖锐且显着的(ANOVA,p值<0.05)下调DME基因的表达,在暴露于氧化铜NPs的小鼠中观察到影响最大。另外,所有NPs均引起肝炎并上调il6基因的表达,其与DMEs的表达呈负相关。可以得出结论,所有测试的NPs下调DME基因的表达,其中氧化铜NPs表现出最大的影响,与肝脏中的炎症和il6基因诱导有关。需要进一步的研究来发现抗炎化合物对抗金属NPs暴露于肝DME引起的改变的作用。

更新日期:2020-06-25
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