Neuroprotective Effects of Engineered Polymeric Nasal Microspheres Containing Hydroxypropyl-β-cyclodextrin on β-Amyloid (1-42)-Induced Toxicity
| Autor: | Guliz Armagan, Elena Soddu, Lutfiye Kanit, Paolo Giunchedi, Giovanna Rassu, Yiğit Uyanıkgil, Ayfer Yalcin, Ezgi Turunc Bayrakdar, Elisabetta Gavini |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pharmaceutical Science DNA Fragmentation Pharmacology medicine.disease_cause Neuroprotection Hippocampus Lipid peroxidation Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Receptor Administration Intranasal chemistry.chemical_classification Reactive oxygen species Amyloid beta-Peptides Neurotoxicity medicine.disease Molecular biology Microspheres Peptide Fragments 2-Hydroxypropyl-beta-cyclodextrin 030104 developmental biology Neuroprotective Agents chemistry Apoptosis DNA fragmentation Neurotoxicity Syndromes Lipid Peroxidation 030217 neurology & neurosurgery Oxidative stress Synaptosomes |
| Zdroj: | Journal of pharmaceutical sciences. 105(8) |
| ISSN: | 1520-6017 |
| Popis: | β-Amyloid (Aβ) plaques are the key neurotoxic assemblies in Alzheimer disease. It has been suggested that an interaction occurs between membrane cholesterol and Aβ aggregation in the brain. Cyclodextrins can remove cholesterol from cell membranes and change receptor function. This study aimed to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-CD) polymeric microspheres, based on chitosan or sodium alginate, on the levels of lipid peroxidation, reactive oxygen species production, and mitochondrial function in brain synaptosomes. The effect of microspheres on DNA fragmentation, the expression of Bcl-2, Bax, and Apex1 mRNAs in rat hippocampus after Aβ(1-42) peptide-induced neurotoxicity was also evaluated. Comparison with HP-CD raw material was performed. Aβ(1-42) treatment significantly decreased the mitochondrial activity of Apex1 and Bcl-2 mRNAs, induced DNA fragmentation, and increased mRNA levels of Bax. Treatment with HP-CD microspheres against Aβ(1-42) significantly reduced DNA fragmentation and increased the Bcl-2/Bax mRNA ratio and mitochondrial function. In addition, HP-CD microspheres used against Aβ(1-42) decreased the levels of lipid peroxidation and reactive oxygen species production. These results indicate that nasally administered spray-dried HP-CD microspheres are able to provide protection against Aβ(1-42)-induced neurotoxicity, due to the suppressed levels of oxidative stress and apoptotic signals in the rat hippocampus. |
| Databáze: | OpenAIRE |
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