Dietary nanoencapsulated quercetin homeostated transcription of redox-status orchestrating genes in zebrafish (Danio rerio) exposed to silver nanoparticles

Abstract

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^-1) 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.

Keywords: Antioxidant enzyme gene; Chitosan; Keap1-Nrf2 pathway; Oxidative stress.