Protective mechanisms of pycnogenol in ethanol-insulted cerebellar granule cells.
Pycnogenol (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), inhibits apoptosis and necrosis of developing neurons exposed acutely to ethanol (EtOH). The present study shows that the protective mechanisms of PYC in EtOH-exposed postnatal day 9 cerebellar granule cells (P9 CGCs) include (1) reduction of reactive oxygen species (ROS) production; (2) counteraction of suppressed copper/zinc superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase/reductase (GSH-Px/GSSG-R) system activities; (3) upregulation of Cu/Zn SOD protein expression; (4) mitigation of the EtOH-mediated exacerbation of catalase (CAT) activity; and, (5) specific binding and inhibition of active caspase-3. These results indicate that the mechanisms by which PYC antagonizes EtOH-induced oxidative stress include oxidant scavenging and modulation of endogenous, cellular proteins. Using findings from the present and previous studies, a model delineating the mechanisms of EtOH effects on the system of antioxidant enzymes in developing CGCs is presented.
Siler-Marsiglio
Kendra I
KI
Department of Neuroscience, University of Florida, McKnight Brain Institute, Gainesville, Florida 32611, USA. kendra@ufl.edu
Paiva
Michael
M
Madorsky
Irina
I
Serrano
Yahaira
Y
Neeley
Andy
A
Heaton
Marieta B
MB
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005419:Flavonoids / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000431:Ethanol; C024070:pycnogenols