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Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Lipophilic Bioactive Compounds Transported in Triglyceride-Rich Lipoproteins Modulate Microglial Inflammatory
Juan M Espinosa1, Jose M Castellano1, Silvia Garcia-Rodriguez1
1Department of Food and Health, Instituto de la Grasa-CSIC, Campus of the University Pablo de Olavide, Building 46, 41012 Seville, Spain.
Abstract:
Microglial cells can contribute to Alzheimer's disease by triggering an inflammatory response that leads to neuronal death. In addition, the presence of amyloid-β in the brain is consistent with alterations in the blood-brain barrier integrity and triglyceride-rich lipoproteins (TRL) permeation. In the present work, we used lab-made TRL as carriers of lipophilic bioactive compounds that are commonly present in dietary oils, namely oleanolic acid (OA), α-tocopherol (AT) and β-sitosterol (BS), to assess their ability to modulate the inflammatory response of microglial BV-2 cells. We show that treatment with lab-made TRL increases the release and gene-expression of IL-1β, IL-6, and TNF-α, as well as NO and iNOS in microglia. On the other hand, TRL revealed bioactive compounds α-tocopherol and β-sitosterol as suitable carriers for oleanolic acid. The inclusion of these biomolecules in TRL reduced the release of proinflammatory cytokines. The inclusion of these biomolecules in TRL reduced the release of proinflammatory cytokines. AT reduced IL-6 release by 72%, OA reduced TNF-α release by approximately 50%, and all three biomolecules together (M) reduced IL-1β release by 35% and TNF-α release by more than 70%. In addition, NO generation was reduced, with the inclusion of OA by 45%, BS by 80% and the presence of M by 88%. Finally, a recovery of the basal glutathione content was observed with the inclusion of OA and M in the TRL. Our results open the way to exploiting the neuro-pharmacological potential of these lipophilic bioactive compounds through their delivery to the brain as part of TRL.
Insights
Triglyceride-rich lipoproteins (TRL) carrying oleanolic acid, α-tocopherol, and β-sitosterol reduced inflammatory responses in microglial cells. This suggests potential for TRL-mediated delivery of neuroprotective compounds for Alzheimer's disease treatment.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Microglial cells contribute to Alzheimer's disease (AD) pathogenesis via inflammatory responses, leading to neuronal death.
- Amyloid-β presence in AD correlates with blood-brain barrier (BBB) dysfunction and altered triglyceride-rich lipoprotein (TRL) permeation.
- Lipophilic bioactive compounds from dietary oils, such as oleanolic acid (OA), α-tocopherol (AT), and β-sitosterol (BS), may possess neuroprotective properties.
Purpose of the Study:
- To investigate the potential of lab-made TRL as carriers for lipophilic compounds (OA, AT, BS).
- To assess the ability of these TRL-encapsulated compounds to modulate microglial inflammatory responses.
- To evaluate the neuro-pharmacological potential of TRL-mediated delivery of these compounds for AD.
Main Methods:
- Cultured microglial BV-2 cells were treated with lab-made TRL.
- TRL were loaded with oleanolic acid (OA), α-tocopherol (AT), and β-sitosterol (BS).
- Pro-inflammatory cytokine release (IL-1β, IL-6, TNF-α), nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and glutathione content were measured.
Main Results:
- Treatment with unloaded TRL increased microglial inflammatory markers (IL-1β, IL-6, TNF-α, NO, iNOS).
- TRL loaded with OA, AT, and BS significantly reduced the release of pro-inflammatory cytokines and NO production.
- Specific reductions included: AT reduced IL-6 by 72%; OA reduced TNF-α by ~50%; OA, AT, BS (M) reduced IL-1β by 35% and TNF-α by >70%. NO generation was reduced by OA (45%), BS (80%), and M (88%).
- Inclusion of OA and M in TRL restored basal glutathione levels, indicating reduced oxidative stress.
Conclusions:
- Lab-made TRL can effectively encapsulate lipophilic bioactive compounds like OA, AT, and BS.
- TRL-mediated delivery of these compounds demonstrates significant anti-inflammatory effects in microglial cells.
- This approach holds promise for exploiting the neuro-pharmacological potential of these compounds for managing neurodegenerative diseases like AD.
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