Effects of Redox Response on Mouse Liver Cells Exposed to L-Buthionine-Sulfoximine and Chitosan-Glutathione Nanoparticles
Journal of Drug Metabolism and Toxicology(2021)
摘要
There is interest in the use of nano materials as drug delivery vehicles or diagnostic systems, able to modulate cellular
responses, which can be easily altered by many factors. Nanoparticles made of chitosan are considered suitable drug
carriers due to their biocompatible properties; on the other hand, glutathione plays an essential role in the
modulation of the redox balance into the cell. Glutathione is the major intracellular antioxidant, with many essential
signaling functions. The depletion of this tripeptide activates several ways implied on the modulation of redox status
that could lead to oxidative stress. Considering the activity of glutathione in various cellular events and the fact that
its synthesis is only generated at the cytoplasmic level, the purpose of this work is to evaluate the ability of
nanoparticles prepared with chitosan and glutathione to modulate redox cell responses on mouse liver cells (AML-12)
exposed to L-Buthionine Sulfoximine (BSO) an inhibitor of the glutathione synthesis. Chitosan-glutathione
nanoparticles were manufactured by ionic gelation then characterized by Transmission Electron Microscopy (TEM),
Dynamic Light Scattering (DLS), and Z potential. The intracellular localization and cytotoxicity nanoparticles
particles were evaluated by confocal microscopy and MTT assays, respectively. The ability to incorporate glutathione
was determined through the intracellular Glutathione content assay, modulating the expression of the transcription
factor Nrf2 and the antioxidant enzyme gene associated with glutathione Grx-1, was quantified using quantitative
real-time PCR. The results showed nanoparticles into the cells and an increase of thiol content where nanoparticles
were present, as well as an increase of the expression of Nrf2 and Grx-1 in a dose-dependent manner.
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关键词
mouse liver cells,l-buthionine-sulfoximine,chitosan-glutathione
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