Dépôt numérique

Donepezil-loaded extracellular vesicles attenuates LPS-induced oxidative stress: in vitro and in vivo studies

Ramassamy, Charles ORCID logoORCID: https://orcid.org/0000-0002-3252-5878; Rummenigge, Silva; Counil, Hermine; Mohamed, Haddad; Zaoutier, Charlotte et Patten, Shunmoogum A. ORCID logoORCID: https://orcid.org/0000-0002-2782-3547 (2023). Donepezil-loaded extracellular vesicles attenuates LPS-induced oxidative stress: in vitro and in vivo studies In: 21st Biennial Congress of the Society-for-Free-Radical-Research-International (SFRRI), November 15-18, 2023, Punta del Este, Uruguay.

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Alzheimer's disease (AD) is the most common neurodegenerative diseases. Oxidative stress has been shown to be a major contributor of the progression of the disease. Donepezil (DNZ) is an FDA-approved acetylcholinesterase inhibitor for AD and has also been shown to reduce reactive oxygen species (ROS) levels in the cortex and hippocampus. Despite this, the drug exhibits extensive first-pass metabolism with poor bioavailability and peripheral adverse events. Extracellular vesicles (EVs) are nanosized vesicles released by almost all cell types in the body, may have lower immunogenicity and high ability to cross the blood-brain barrier. The aim of this work was to load DNZ in plasma-derived EVs (pEV-DNZ) or released by mesenchymal stem cells (MSC-EV-DNZ). Their antioxidant potential was analyzed using the fluorescent probe DCFH-DA in the presence of LPS. The sizes of the pEV-DNZ and MSC-EV-DNZ were, respectively, 119.3 ± 0.74 nm and 162.7 ± 1.18 nm, respectively. LPS treatment at 1 μg/mL for 24 h induced an elevation of ROS in the human microglial HMC3 cells. Interestingly, we demonstrated that ROS production was reduced by treating cells with DNZ-loaded EVs. The protective effects of nanoformulations were also evaluated in zebrafish embryos. Embryos of 2 dpf were incubated for 24h with LPS (10 μg/mL) with or without the formulations and the production of ROS was analyzed by confocal microscopy. pEVs and MSC-EV-DNZ treatment reduced the levels of ROS. Interestingly, a greater reduction in ROS was observed in zebrafish larvae treated with pEV-DNZ. These results suggest that the protective effect against LPS is higher with DNZ-loaded EVs. Support: Research Chair on Alzheimer’s disease.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique 362 Free Radical Biology and Medicine 208 (suppl. 1) S164-S164
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 04 janv. 2024 14:43
Dernière modification: 04 janv. 2024 14:43
URI: https://espace.inrs.ca/id/eprint/13962

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