Caffeic acid phenethyl ester blocks free radical generation and 6-hydroxydopamine-induced neurotoxicity.
Neurotoxicity induced by 6-hydroxydopamine (6-OHDA) is believed to be due, in part, to the production of reactive oxygen species (ROS). Antioxidants protect neurons against 6-OHDA-induced neurotoxicity by inhibiting free radical generation. In this study, we investigated whether or not caffeic acid phenethyl ester (CAPE) could protect neurons against 6-OHDA-induced neurotoxicity in cultured rat rostral mesencephalic neurons (RMN) and cerebellar granule neurons (CGN). We now report that exposure of RMN and CGN to 6-OHDA (40 microM for RMN and 70 microM for CGN) resulted in significant increases in free radical production and death of both neuron types. Pretreatment with CAPE (10 microM) for 2 h prevented both 6-OHDA-induced free radical generation and neurotoxicity. Furthermore, CAPE also attenuated H(2)O(2)-induced neurotoxicity. Our results strongly suggest that CAPE blocks 6-OHDA-induced neuronal death possibly by inhibiting 6-OHDA-induced free radical generation and blocking free radical-induced neurotoxicity in neurons. Both the antioxidative and neuroprotective effects of CAPE may be beneficial in the therapy for Parkinson's disease and other neurodegenerative diseases.
Ma
Zhizhong
Z
Department of Neurology, Indiana University School of Medicine, 975 West Walnut Street, Rm 457, Indianapolis, IN 46202, USA.
Wei
Xing
X
Fontanilla
Christine
C
Noelker
Carmen
C
Dodel
Richard
R
Hampel
Harald
H
Du
Yansheng
Y
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants; D002109:Caffeic Acids / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D030421:Peroxynitrous Acid / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000633:toxicity*
D000975:Antioxidants; D002109:Caffeic Acids; D005609:Free Radicals; D013565:Sympatholytics; D030421:Peroxynitrous Acid; D016627:Oxidopamine; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol