Protection of primary glial cells by grape seed proanthocyanidin extract against nitrosative/oxidative stress

Citation
S. Roychowdhury et al., Protection of primary glial cells by grape seed proanthocyanidin extract against nitrosative/oxidative stress, NITRIC OXID, 5(2), 2001, pp. 137-149
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
ISSN journal
1089-8603 → ACNP
Volume
5
Issue
2
Year of publication
2001
Pages
137 - 149
Database
ISI
SICI code
1089-8603(200104)5:2<137:POPGCB>2.0.ZU;2-5
Abstract
Previous studies showed that proanthocyanidins provide potent protection ag ainst oxidative stress. Here we investigate the effects of grape seed proan thocyanidin extract (GSPE) as a novel natural antioxidant on the generation and fate of nitric oxide (NO) in rat primary glial cell cultures, GSPE tre atment (50 mg/L) increased NO production (measured by NO2- assay) by stimul ation of the inducible isoform of NOS. However, G;SPE failed to affect the LPS/IFN-gamma -induced NO production or iNOS expression. Similar responses were found in the murine macrophage cell line RAW264.7. GSPE did not show a ny effect on dihydrodichlorofluorescein fluorescence (ROS marker with high sensitivity toward peroxynitrite) either in control or in LPS/IFN-gamma -in duced glial cultures even in the presence of a superoxide generator (PMA). C;SPE treatment alone had no effect on the basal glutathione (GSH) status i n glial cultures. Whereas the microglial GSH level declined sharply after L PS/IFN-gamma treatment, the endogenous GSH pool was protected when such cul tures were treated additionally with GSPE, although NO levels did not chang e. Glial cultures pretreated with GSPE showed higher tolerance toward appli cation of hydrogen peroxide (H2O2) and tert-butylhydroperoxide. Furthermore , GSPE-pretreated glial cultures showed improved viability after H2O2-induc ed oxidative stress demonstrated by reduction in lactate dehydrogenase rele ase or propidium iodide staining. We showed that, in addition to its antiox idative property, GSPE enhances low-level production of intracellular NO in primary rat astroglial cultures. Furthermore, GSPE pretreatment protects t he microglial GSH pool during high output NO production and results in an e levation of the H2O2 tolerance in astroglial cells. (C) 2001 Academic Press .