Hepatotoxicity and nephrotoxicity of quercetin, iron oxide nanoparticles, and quercetin conjugated with nanoparticles in rats

Kazemipour, Nasrin; Nazifi, Saeed; Poor, Mir Hossein Hashemi; Esmailnezhad, Z.; Najafabadi, Rezvan Enteshari; Esmaeili, Abolghasem

doi:10.1007/s00580-018-2783-5

Cited by 15 publications

(10 citation statements)

References 50 publications

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“…We believe that an increase in the total antioxidant level in the diabetic group could be due to an increase in potential composition of different antioxidants, which is the key for intervention to counteract ROS induced damage and diabetic neuropathy progression. In addition, this finding is in agreement with our previous report which showed both QC and QCSPIONs groups (50 mg/kg and 100 mg/kg) didn't show any change in hepatic TAC, GSH, MDA levels, and CAT activity of intact/ healthy rats 46 . Besides, we investigated the antitoxic effects of QC and QCSPIONs against H2O2-induced toxicity in PC12 cells in a separate study.…”

Section: Discussionsupporting

confidence: 93%

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

Ebrahimpour

Shahidi

Abbasi

et al. 2020

Sci Rep

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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.

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Section: Discussionsupporting

confidence: 93%

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

Ebrahimpour

Shahidi

Abbasi

et al. 2020

Sci Rep

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“…We believe that an increase in the total levels of hippocampal antioxidants during hyperglycemia is the key for intervention to counteract ROS. In addition, this result is in line with our previous report that showed both QC and QCSPION groups (50 mg/kg and 100 mg/kg) did not display any alteration in hepatic GSH, MDA, TAC levels, and CAT activity of intact/healthy rats [45]. From these studies, it can be concluded that nanoparticles with minimal toxicity on the liver enzymes and Total Antioxidant Capacity possibly will be used as a drug delivery system in neurodegenerative diseases.…”

Section: Jiang Et Al (2010) Revealed a Reduction In Nrf2 Expression Osupporting

confidence: 91%

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

Ebrahimpour¹,

Shahidi²,

Aabbasi³

et al. 2020

Preprint

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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.

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“…This study did not show a significant difference in hepatic and renal AST, ALT, ALP, GGT, and LDH activities between control and treated groups. 55 In these studies, the concentration of QC in the conjugated form was significantly lower than free QC concentration because only one part of the construct was composed of QC. Therefore, we can propose that the lower dosage of QC in the conjugate state could have a higher potential than pure QC.…”

Section: Discussionmentioning

confidence: 99%

Effect of quercetin-conjugated superparamagnetic iron oxide nanoparticles on diabetes-induced learning and memory impairment in rats

Ebrahimpour

Esmaeili

Beheshti

2018

IJN

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BackgroundDiabetes mellitus plays a causative role in cognitive decline. Newly, neuroprotective effects of flavonoids have been widely investigated in neurodegenerative diseases. Quercetin (QC) is a phyto-derived bioactive flavone with numerous beneficial activities. However, its limited permeability to cross the blood–brain barrier, low oral bioavailability, poor aqueous solubility, and rapid gastrointestinal digestion lead to the administration of high dose of QC in clinical application.Materials and methodsIn order to overcome these limitations, we conjugated QC with superparamagnetic iron oxide nanoparticles (QCSPIONs) and supplemented streptozotocin-induced diabetic rats with it to improve diabetes-related memory impairment. In this regard, 40 rats were distributed into five groups with eight animals: control, diabetes, and diabetes treated with SPIONs, QC, and QCSPIONs. All treatments (at the dose of 25 mg/kg) were dissolved in deionized water and gavaged for 35 consecutive days.ResultsAt the end of the study, QCSPIONs possessed significantly better efficacy than free QC on the improvement of memory performance. In the Morris water maze test, QCSPIONs compared to free QC reduced much better the escape latency over training trials (P<0.01) and increased the time spent in the target quadrant in probe trial (P<0.001). In the passive avoidance test, it increased step-through latency (P<0.05) and reduced the time spent in the dark compartment (P<0.01). In addition, both free QC and QCSPIONs were able to prevent the changes in body weight and decrease blood glucose levels in diabetic rats (P<0.05).ConclusionOverall, according to these results, we conclude that QC in the conjugated state with lower dose offers significantly higher potency in ameliorating diabetes-related memory impairment. Thus, this study offers an effective combined therapy for improving learning and memory.

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Hepatotoxicity and nephrotoxicity of quercetin, iron oxide nanoparticles, and quercetin conjugated with nanoparticles in rats

Cited by 15 publications

References 50 publications

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

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

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

Effect of quercetin-conjugated superparamagnetic iron oxide nanoparticles on diabetes-induced learning and memory impairment in rats

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