Abstract
Oxidative stress is one of the earliest defects involved in the development of diabetes-induced cognitive impairment. Nrf2 is the master regulator of the cellular antioxidant system can be regulated by some microRNAs. The study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes through the redox-sensitive miR-27a. Expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT were measured by quantitative real-time PCR. Moreover, the oxidative stress parameters including total antioxidant capacity (TAC) and histological alterations were investigated. The expression level of miR-27a was significantly up-regulated in diabetic rats. While expression levels of Nrf2, SOD1, GPX1, and CAT were significantly down-regulated under diabetic condition. Interestingly, QCSPIONs decreased expression level of miR-27a and subsequently enhanced the expression levels of Nrf2, SOD1, and CAT to the control level. No significant difference was observed in the expression level of GPX1. Besides, QC in pure and especially conjugated form was able to normalize TAC and regenerate pathological lesions in STZ-diabetic rats. Our result demonstrates that QCSPIONs as an effective combined therapy can decrease miR-27a expression, which in turn increases the Nrf2 expression and responsive antioxidant genes, resulting in improvement of memory dysfunction in diabetic rats.
Highlights
Diabetes mellitus (DM) is the most common chronic metabolic disorder characterized by persistent hyperglycemia associated with lipid, protein, and carbohydrate metabolism abnormalities[1]
Diabetes-related cognitive dysfunction can seriously challenge the demand for future health resources, so understanding the pathophysiology of the disorder and identifying molecular pathways that can lead to improved therapy in the future are urgent[28]
We showed that diabetes causes memory impairment during 45 days in male Wistar rats
Summary
Diabetes mellitus (DM) is the most common chronic metabolic disorder characterized by persistent hyperglycemia associated with lipid, protein, and carbohydrate metabolism abnormalities[1]. Emerging studies reported that QC presented beneficial effects against various diseases through influencing directly gene expression at an epigenetic or transcriptional level and by modulating miRNAs as part of the post-transcriptional regulation of genes[21]. Despite these favorable properties, its bioavailability to the brain is low owing to poor solubility, stability, and distribution so various conjugates of QC have been developed to overcome these limitations[16,22]. This study aimed to compare the effect of pure QC and QCSPIONs on the expression of miR-27a, Nrf[2], SOD1, GPX1, and CAT genes as well as the histological alteration in multiple low-dose streptozotocin (MLDS)-induced diabetic rats
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