Resveratrol is a dietary
polyphenol that displays neuroprotective properties in several in vivo and in vitro experimental models, by modulating oxidative and inflammatory responses.
Glutathione (GSH) is a key
antioxidant in the central nervous system (CNS) that modulates several cellular processes, and its depletion is associated with oxidative stress and
inflammation. Therefore, this study sought to investigate the protective effects of
resveratrol against GSH depletion pharmacologically induced by
buthionine sulfoximine (BSO) in C6 astroglial cells, as well as its underlying cellular mechanisms. BSO exposure resulted in several detrimental effects, decreasing
glutamate-cysteine ligase (GCL) activity,
cystine uptake, GSH intracellular content and the activities of the
antioxidant enzymes glutathione peroxidase (GPx) and
glutathione reductase (GR). Moreover, BSO increased reactive
oxygen/
nitrogen species (ROS/RNS) levels and pro-inflammatory
cytokine release.
Resveratrol prevented these effects by protecting astroglial cells against BSO-induced cytotoxicity, by modulating oxidative and inflammatory responses. Additionally, we observed that pharmacological inhibition of
heme oxygenase 1 (HO-1), an essential cellular defense against oxidative and inflammatory
injuries, abolished all the protective effects of
resveratrol. These observations suggest HO-1 pathway as a cellular effector in the mechanism by which
resveratrol protects astroglial cells against GSH depletion, a condition that may be associated to
neurodegenerative diseases.