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
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. Th...
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MDPI AG
2022-07-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/8/918 |
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| author | Medhat Taha Sara T. Elazab Alaa. M. Badawy Abdullah A. Saati Naeem F. Qusty Abdullah G. Al-Kushi Anas Sarhan Amira Osman Amira E. Farage |
| author_facet | Medhat Taha Sara T. Elazab Alaa. M. Badawy Abdullah A. Saati Naeem F. Qusty Abdullah G. Al-Kushi Anas Sarhan Amira Osman Amira E. Farage |
| author_sort | Medhat Taha |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T03:59:29Z |
| format | Article |
| id | doaj.art-6b5ec0cea35244efac57e71efd9f739a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T03:59:29Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-6b5ec0cea35244efac57e71efd9f739a2023-12-03T14:15:59ZengMDPI AGPharmaceuticals1424-82472022-07-0115891810.3390/ph15080918Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and ApoptosisMedhat Taha0Sara T. Elazab1Alaa. M. Badawy2Abdullah A. Saati3Naeem F. Qusty4Abdullah G. Al-Kushi5Anas Sarhan6Amira Osman7Amira E. Farage8Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Community Medicine and Pilgrims Healthcare, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi ArabiaMedical Laboratories Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 24382, Saudi ArabiaDepartment of Human Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi ArabiaDepartment of Internal Medicine, College of Medicine, Umm Al-Qura University, Makkah 24382, Saudi ArabiaDepartment of Histology, Faculty of Medicine, Kafrelsheikh University, Kafr Elsheikh 33511, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine, Kafrelsheikh University, Kafr Elsheikh 33511, EgyptChemo 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.https://www.mdpi.com/1424-8247/15/8/918cerium oxide nanoparticlesdoxorubicinchemobrainoxidative stresssynaptic plasticity |
| spellingShingle | Medhat Taha Sara T. Elazab Alaa. M. Badawy Abdullah A. Saati Naeem F. Qusty Abdullah G. Al-Kushi Anas Sarhan Amira Osman Amira E. Farage 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 Pharmaceuticals cerium oxide nanoparticles doxorubicin chemobrain oxidative stress synaptic plasticity |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | cerium oxide nanoparticles doxorubicin chemobrain oxidative stress synaptic plasticity |
| url | https://www.mdpi.com/1424-8247/15/8/918 |
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