WITHDRAWN: Quercetin-conjugated superparamagnetic iron oxide nanoparticles enhances Nrf2 expression through miR-27a intervention to prevent memory dysfunction in diabetic rats

Abstract

Background: Oxidative stress is involved in the development of diabetes-induced cognitive impairment. Nrf2 as a redox-sensing gene can be regulated by some microRNAs. This study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes via the miR-27a. Streptozotocin was applied to produce type 1 diabetes in male Wistar rats. Animals (five groups of 8 rats) were treated for 35 days. Real-time polymerase chain reaction method was applied to assess the expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT. Moreover, total antioxidant capacity (TAC) and histological alterations were investigated. Results: A significant up-regulation in the expression level of miR-27a was observed in diabetic rats in comparison to control (p<0.01). The mRNA expression levels of Nrf2, SOD1, GPX1 and CAT were significantly down-regulated under diabetic condition (p<0.0001, p<0.01, p<0.0001 and p<0.0001, respectively). Interestingly, QCSPIONs decreased expression level of miR-27a (p<0.01) and subsequently enhanced the expression levels of the Nrf2 (P<0.5), SOD1 (P<0.0204) and CAT (P<0.01) to the control level. Significant difference was not recognized in the expression level of GPX1 under QCSPIONs treatment. In addition, QC in pure and especially conjugated form was able to normalize TAC (p<0.01) and regenerate pathological lesions in STZ-diabetic rats. Conclusions: Result demonstrates that QCSPIONs as an effective combined therapy can reduce the miR-27a expression, that in turn increases the mRNA Nrf2 expression and its responsive antioxidant genes, resulting in the prevention of diabetic complications.

Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats

“…iron determination in brain. To measure the concentration of iron in the brain tissue, inductively coupled plasma-atomic emission spectrometry (ICP-AES, ICPS-7500, Shimadzu, Japan) was used 56,57 . The equal amount of brain sections were prepared and treated with HNO3 (65%) for 16 h at room temperature and were filtered www.nature.com/scientificreports/ until a transparent solution was obtained.…”