Intranasal Cerium Oxide Nanoparticles Ameliorate Cognitive Function in Rats with Alzheimer’s via Anti-Oxidative Pathway

Danish, Syed Noman; Gupta, Anshul; Khan, Urooj A; Hasan, Nazeer; Ahmad, Farhan Jalees; Warsi, Musarrat Husain; Ali, Ahmed Mahmoud Abdelhaleem; Zafar, Ameeduzzafar; Jain, Gaurav

doi:10.3390/pharmaceutics14040756

Cited by 20 publications

(13 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This anti-amnestic effect of the CeNP may be owed to the amelioration of the histological changes in the hippocampus, as reflected by the decreasing percent of degenerated neurons. This neuroprotective effect of CeNPs is in line with the findings of Danish et al [ 41 ], who stated that the intranasal administration of CeNPs markedly improved the cognitive function of the scopolamine-induced model of Alzheimer disease.…”

Section: Discussionsupporting

confidence: 90%

Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis

et al. 2022

View full text Add to dashboard Cite

Chemo fog is one of the most serious health concerns encountered by cancer survivors receiving doxorubicin (DOX)-based chemotherapy. Oxidative stress, neuroinflammation, apoptosis and impairment of synaptic plasticity are regarded as the key factors implicated in DOX-induced cognitive impairment. This research aimed to assess the possible neuroprotective effect of cerium oxide nanoparticles (CeNPs) against DOX-induced neurotoxicity. Forty-eight rats were divided into four groups (12 rats/group): control group, CeNPs group (received oral CeNPs solution (35 mg/kg) daily for 4 weeks), and DOX group (were administered DOX intraperitoneally (2 mg/kg, once/week for 4 weeks)) and DOX+ CeNPs group. The findings revealed that CeNPs mitigated behavioral alterations in DOX-induced cognitive deficit. Additionally, CeNPs alleviated the histopathological abnormalities in hippocampus and ameliorated DOX-induced neuroinflammation by downregulating the expression of NF-κB, TNF-α, IL-1β and IL6. In addition, CeNPs antagonized the apoptosis through reducing the protein expression of cytochrome c and caspase 3. In addition, it stimulated the antioxidant defense, as indicated by upregulating the expression of the Nrf2, HO-1 and PGC-1α genes. CeNPs improved synaptic plasticity via acting on the BDNF. These actions were related through the modification of SIRT-1 expression. Based on the aforementioned results, CeNPs antagonized the doxorubicin-induced neurodegeneration by its antioxidant, anti-inflammatory and antiapoptotic effects, alongside its SIRT-1 mediated mechanisms.

show abstract

Section: Discussionsupporting

confidence: 90%

Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The pathogenesis of PD profoundly relies on oxidative stress, which lead to neuroinflammation and subsequently neurodegeneration of the brain ( Hwang, 2013 ). The antioxidant potential of CONPs is well established and we recently reported promising effects of intranasal CONPs in the treatment of AD ( Danish et al, 2022 ). In the present study, we assessed the therapeutic potential of intranasal CONPs in haloperidol-induced PD model.…”

Section: Discussionmentioning

confidence: 99%

“…CONPs were prepared by modification of previously published homogenous precipitation method ( Danish et al, 2022 ). Briefly, tween 80 was dissolved in methanol: water solution (20 mL) and to this cerium (III) nitrate hexahydrate was added.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the results demonstrated that NPs immediately enter into the CSF by subarachnoid absorption by the nasal epithelium ( Bonferoni et al, 2020 ). Recently, intranasal CONPs prepared in our lab have shown therapeutic potential for the management of AD ( Danish et al, 2022 ). Though, the efficacy of CONPs in PD is extensively reported, we hypothesized that intranasal administration might result in targeted brain delivery leading to reduced dose, improved efficacy and reduced side-effects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats

Mohammad,

Khan,

Warsi

et al. 2023

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Introduction: Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson’s disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration.Method: The antioxidant potential of the CONPs was evaluated in vitro using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated ex-vivo using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model.Results: The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25 μg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant (p < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high (p < 0.001) dopamine concentration (13.93 ± 0.85 ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70 ng/mg protein).Conclusion: The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.

show abstract

“…These mechanisms can protect neurons from neurodegeneration and promote their survival. In AD, CNPs have been investigated as a potential therapeutic agent due to their neuroprotective effects ( Danish et al, 2022 ). CNPs have been shown to reduce Aβ-induced toxicity in vitro and in vivo by reducing oxidative stress, inflammation, and Aβ aggregation.…”

Section: Introductionmentioning

confidence: 99%

The effect of cerium dioxide nanoparticles on the viability of hippocampal neurons in Alzheimer’s disease modeling

Hanzha

Rozumna²,

Kravenska³

et al. 2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The possibilities of using nanoparticle materials based on cerium dioxide (CNPs) are exciting since they are low toxic and have specific redox, antiradical properties. It can be supposed that CNPs’ biomedical use is also relevant in neurodegenerative diseases, especially Alzheimer’s disease (AD). AD is known as the pathologies leading to progressive dementia in the elderly. The factor that provokes nerve cell death and cognitive impairment in AD is the pathological accumulation of beta-amyloid peptide (Aβ) in the brain tissue. In our studies, we examined the impact of Aβ 1-42 on neuronal death and evaluated the potential neuroprotective properties of CNPs during AD modeling in cell culture. Our findings show that, under AD modeling conditions, the number of necrotic neurons increased from 9.4% in the control to 42.7% when Aβ 1-42 was used. In contrast, CNPs alone showed low toxicity, with no significant increase in the number of necrotic cells compared to control conditions. We further explored the potential of CNPs as a neuroprotective agent against Aβ-induced neuronal death. We found that introducing CNPs 24 h after Aβ 1-42 incubation or prophylactically incubating hippocampal cells with CNPs 24 h before amyloid administration significantly reduced the percentage of necrotic cells to 17.8 and 13.3%, respectively. Our results suggest that CNPs in the cultural media can significantly reduce the number of dead hippocampal neurons in the presence of Aβ, highlighting their neuroprotective properties. These findings suggest that CNPs may hold promise for developing new treatments for AD based on their neuroprotective properties.

show abstract

Intranasal Cerium Oxide Nanoparticles Ameliorate Cognitive Function in Rats with Alzheimer’s via Anti-Oxidative Pathway

Cited by 20 publications

References 31 publications

Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis

Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats

The effect of cerium dioxide nanoparticles on the viability of hippocampal neurons in Alzheimer’s disease modeling

Contact Info

Product

Resources

About