Effects of epigallocatechin gallate on rotenone-injured murine brain cultures.
Green tea polyphenol epigallocatechin-3-gallate (EGCG) is reported to have antioxidant abilities and to counteract beneficially mitochondrial impairment and oxidative stress. The present study was designed to investigate neuroprotective effects of EGCG on rotenone-treated dissociated mesencephalic cultures and organotypic striatal cultures. Rotenone is a potent inhibitor of complex I of the respiratory chain, which in vitro causes pathological and neurochemical characteristics of diseases in which mitochondrial impairment is involved, e.g., Parkinson's disease. Treatment with EGCG (0.1, 1, 10 muM) alone had no significant effects on mesencephalic cultures. In striatal slice cultures, EGCG led to a significant increase of propidium iodide (PI) uptake and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM), but not dihydroethidium (DHE) fluorescence intensity. Rotenone (20 nM on the eighth DIV for 48 h) significantly decreased the numbers and the neurite lengths of TH ir neurons by 23 and 34% in dissociated mesencephalic cell cultures compared to untreated controls. Exposure of striatal slices to rotenone (0.5 mM for 48 h) significantly increased PI uptake, and DAF-FM and DHE fluorescence intensities by 41 and 136 and 19%, respectively, compared to controls. Against rotenone, in dissociated mesencephalic cultures, EGCG produced no significant effect on either the number or neurite lengths of THir neurons compared to rotenone-treated cultures, but EGCG significantly decreased PI uptake by 19% and DAF-FM fluorescence intensity by 19 and 58%, respectively, compared to increase in rotenone-exposed striatal slices. On the other hand, EGCG did not affect superoxide (O(2) (-)) formation as detected with DHE. These data indicate that EGCG slightly protects striatal slices by counteracting nitric oxide (NO(.)) production by rotenone. In conclusion, EGCG partially protects striatal slices but not dissociated cells against rotenone toxicity.
Moldzio
Rudolf
R
Institute for Medical Chemistry, University for Veterinary Medicine, Veterinaerplatz 1, 1210, Vienna, Austria. rudolf.moldzio@vu-wien.ac.at
Radad
Khaled
K
Krewenka
Christopher
C
Kranner
Barbara
B
Duvigneau
Johanna Catharina
JC
Wang
Yingzi
Y
Rausch
Wolf-Dieter
WD
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D008636:Mesencephalon / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D012402:Rotenone; D013481:Superoxides / Q000378:metabolism; D046509:Tissue Culture Techniques; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018696:Neuroprotective Agents; D012402:Rotenone; D013481:Superoxides; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D014446:Tyrosine 3-Monooxygenase
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