Back to Search
Start Over
Glial metabolism of quercetin reduces its neurotoxic potential.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2008 Oct 15; Vol. 478 (2), pp. 195-200. Date of Electronic Publication: 2008 Jul 23. - Publication Year :
- 2008
-
Abstract
- The neuroprotective effects of flavonoids will ultimately depend on their interaction with both neuronal and glial cells. In this study, we show that the potential neurotoxic effects of quercetin are modified by glial cell interactions. Specifically, quercetin is rapidly conjugated to glutathione within glial cells to yield 2'-glutathionyl-quercetin, which is exported from cells but has significantly reduced neurotoxicity. In addition, quercetin underwent intracellular O-methylation to yield 3'-O-methyl-quercetin and 4'-O-methyl-quercetin, although these were not exported from glia at the same rate as the glutathionyl adduct. The neurotoxic potential of both quercetin and 2'-glutathionyl-quercetin paralleled their ability to modulate the pro-survival Akt/PKB and extracellular signal-regulated kinase (ERK) signalling pathways. These data were supported by co-culture investigation, where the neurotoxic effects of quercetin were significantly reduced when they were cultured alongside glial cells. We propose that glial cells act to protect neurons against the neurotoxic effects of quercetin and that 2'-glutathionyl-quercetin represents a novel quercetin metabolite.
- Subjects :
- Animals
Biotransformation
Cell Survival drug effects
Cells, Cultured
Mice
Neuroglia cytology
Neuroprotective Agents metabolism
Neuroprotective Agents pharmacokinetics
Neuroprotective Agents pharmacology
Neurotoxins pharmacokinetics
Quercetin pharmacokinetics
Neuroglia drug effects
Neuroglia metabolism
Neurotoxins metabolism
Neurotoxins toxicity
Quercetin metabolism
Quercetin toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0384
- Volume :
- 478
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 18675775
- Full Text :
- https://doi.org/10.1016/j.abb.2008.07.014