Department of Marine Sciences, Tarbiat Modares University, Mazandaran, Noor, Iran.
Department of Fisheries and Environmental Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran.
Environ Res. 2020 Jun;185:109477. doi: 10.1016/j.envres.2020.109477. Epub 2020 Apr 6.
The present study assessed the protective effect of chitosan-nanoencapsulated quercetin (Qu-ChiNPs) against oxidative stress caused by silver nanoparticles (AgNPs). To this end, the transcription of prime genes regulating hepatic Keap1-Nrf2 pathway as well as downstream antioxidant enzymes were monitored prior to and after oxidative stress by AgNPs. Zebrafish (Danio rerio; n = 225) was assigned into five experimental groups based on feeding with diets supplemented with different additives as follows: negative and positive control groups, without additive; ChiNPs, 400 mg nanochitosan per kg diet; Quercetin, 400 mg free quercetin per kg diet; and Qu-ChiNPs, 400 mg Qu-ChiNPs per kg diet. At the end of the feeding trial (40 days), the experimental groups, except the negative control, were exposed to sublethal concentration of AgNPs (0.15 mg L) for 96h. Before exposure to AgNPs, free quercetin-treated diet significantly upregulated Keap1, Nrf2, Cat, SOD, GPx, and GST genes in the liver tissue when compared with the control diet, whereas Qu-Chi.NPs downregulated their transcription to the lowest levels. After exposure to AgNPs, all genes exhibited different responses in the AgNPs-exposed groups. The highest transcription of Nrf2, Cat, SOD, GPx, and GST was observed in the positive group, with being upregulated about 8, 10, 8, 8, and 7 times, respectively, when compared to the respective ones in the negative control. However, Keap1 showed a reverse response with being transcripted 12 times lower. The quercetin treatments, especially Qu-Chi.NPs, significantly reduced the transcription of Nrf2, Cat, SOD, GPx, and GST genes, yet enhanced Keap1 expression. Qu-Chi.NPs reduced the expression of Nrf2, SOD, Cat, GPx, and GST about 11, 10, 15, 10, and 10 times, respectively, yet increased that of Keap1 about 12 times. Taken together, nanoencapsulation can improve the antioxidant efficacy of quercetin against AgNPs toxicity and might reduce involvement of the cellular antioxidant system through tuning redox status. More broadly, it would be interesting to assess the effects of Qu-Chi.NPs against other metallic and organic oxidative stressors or pollutants.
本研究评估了壳聚糖-纳米封装槲皮素（Qu-ChiNPs）对银纳米颗粒（AgNPs）引起的氧化应激的保护作用。为此，在 AgNPs 引起氧化应激之前和之后，通过监测调节肝 Keap1-Nrf2 途径的主要基因以及下游抗氧化酶的转录来监测。根据添加不同添加剂的饮食进行喂养，将斑马鱼（Danio rerio；n=225）分为五个实验组，如下所示：阴性和阳性对照组，无添加剂；ChiNPs，每公斤饮食中添加 400mg 纳米壳聚糖；槲皮素，每公斤饮食中添加 400mg 游离槲皮素；和 Qu-ChiNPs，每公斤饮食中添加 400mg Qu-ChiNPs。在喂养试验结束时（40 天），除阴性对照组外，其余实验组均暴露于亚致死浓度的 AgNPs（0.15mg L）96h。在暴露于 AgNPs 之前，与对照饮食相比，游离槲皮素处理的饮食显著上调了肝脏组织中的 Keap1、Nrf2、Cat、SOD、GPx 和 GST 基因，而 Qu-Chi.NPs 将其转录下调至最低水平。暴露于 AgNPs 后，AgNPs 暴露组的所有基因均表现出不同的反应。阳性组中 Nrf2、Cat、SOD、GPx 和 GST 的转录水平最高，分别上调约 8、10、8、8 和 7 倍，与阴性对照组相比。然而，Keap1 表现出相反的反应，转录水平低 12 倍。槲皮素处理，特别是 Qu-Chi.NPs，显著降低了 Nrf2、Cat、SOD、GPx 和 GST 基因的转录，同时增强了 Keap1 的表达。Qu-Chi.NPs 将 Nrf2、SOD、Cat、GPx 和 GST 的表达分别降低约 11、10、15、10 和 10 倍，而 Keap1 的表达增加约 12 倍。总之，纳米封装可以提高槲皮素对 AgNPs 毒性的抗氧化功效，并通过调节氧化还原状态来减少细胞抗氧化系统的参与。更广泛地说，评估 Qu-Chi.NPs 对其他金属和有机氧化应激源或污染物的影响将是有趣的。
