Journal du métabolisme des médicaments et de la toxicologie
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Effects of Redox Response on Mouse Liver Cells Exposed to L-Buthionine Sulfoximine and Chitosan-Glutathione Nanoparticle

Sofia Pina-Olmos1, Patricia Ramirez-Noguera1, J. H. Limon-Pacheco2, Maria E. Gonsebatt-Bonaparte2, Denise LopezBarrera, Raul Diaz-Torres*

There is interest in the use of nanomaterials 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 were evaluated by confocal microscopy and MTT assays, respectively. The ability to incorporate glutathione was determined through the intracellular GSH 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.