Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats
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 haloperid...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1188470/full |
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| author | Mohammad Urooj Ahmed Khan Musarrat Husain Warsi Huda Mohammed Alkreathy Shahid Karim Gaurav Kumar Jain Gaurav Kumar Jain Asgar Ali |
| author_facet | Mohammad Urooj Ahmed Khan Musarrat Husain Warsi Huda Mohammed Alkreathy Shahid Karim Gaurav Kumar Jain Gaurav Kumar Jain Asgar Ali |
| author_sort | Mohammad |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-96102fb6c1c9459791bd9d821ade09f6 |
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| language | English |
| last_indexed | 2024-03-13T08:04:25Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-96102fb6c1c9459791bd9d821ade09f62023-06-01T09:02:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11884701188470Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats Mohammad0Urooj Ahmed Khan1Musarrat Husain Warsi2Huda Mohammed Alkreathy3Shahid Karim4Gaurav Kumar Jain5Gaurav Kumar Jain6Asgar Ali7Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, IndiaDepartment of Pharmaceutics, Dr. Ram Manohar Lohia College of Pharmacy, Ghaziabad, Uttar Pradesh, IndiaDepartment of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif, Saudi ArabiaDepartment of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, New Delhi, IndiaCenter for Advanced Formulation Technology, Delhi Pharmaceutical Sciences and Research University, New Delhi, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, IndiaIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fphar.2023.1188470/fullParkinson diseasebrain targetingantioxidant activitygamma scintigraphyinorganic nanoparticles |
| spellingShingle | Mohammad Urooj Ahmed Khan Musarrat Husain Warsi Huda Mohammed Alkreathy Shahid Karim Gaurav Kumar Jain Gaurav Kumar Jain Asgar Ali Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats Frontiers in Pharmacology Parkinson disease brain targeting antioxidant activity gamma scintigraphy inorganic nanoparticles |
| title | Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats |
| title_full | Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats |
| title_fullStr | Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats |
| title_full_unstemmed | Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats |
| title_short | Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats |
| title_sort | intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol induced parkinsonism in rats |
| topic | Parkinson disease brain targeting antioxidant activity gamma scintigraphy inorganic nanoparticles |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1188470/full |
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