Document Detail

Aggravation of L-DOPA-induced neurotoxicity by tetrahydropapaveroline in PC12 cells.
MedLine Citation:
PMID:  14563489     Owner:  NLM     Status:  MEDLINE    
Tetrahydropapaveroline (THP) is formed in Parkinsonian patients receiving L-DOPA therapy and is detected in the plasma and urine of these patients. In this study, we have investigated the effects of THP on L-DOPA-induced neurotoxicity in cultured rat adrenal pheochromocytoma, PC12 cells. Exposure of PC12 cells up to 10 microM THP or 20 microM L-DOPA after 24 or 48 hr, neither affected the cell viability determined by MTT assay, nor induced apoptosis by flow cytometry and TUNEL staining. However, at concentrations higher than 15 microM, THP showed cytotoxicity through an apoptotic process. In addition, THP at 5-15 microM for both incubation time points significantly enhanced L-DOPA-induced neurotoxicity (L-DOPA concentration, 50 microM). Exposure of PC12 cells to THP, L-DOPA and THP plus L-DOPA for 48 hr resulted in a marked increase in the cell loss and percentage of apoptotic cells compared with exposure for 24hr. The enhancing effects of THP on L-DOPA-induced neurotoxicity were concentration- and treated-time-dependent. THP, L-DOPA and THP plus L-DOPA produced a significant increase in intracellular reactive oxygen species generation and decrease in ATP levels, supporting the involvement of oxidative stress in THP- and L-DOPA-induced apoptosis. The antioxidant N-acetyl-L-cysteine strongly inhibited changes in apoptosis, decreases in cell viability and ROS generation induced by THP associated with L-DOPA. These results suggest that THP aggravates L-DOPA-induced oxidative neurotoxic and apoptotic effects in PC12 cells. Therefore, Parkinsonian patients treated with L-DOPA for long-term need to be monitored for the relationship between plasma concentration of THP and the symptoms of neurotoxicity.
Jae Joon Lee; Yu Mi Kim; Shou Yu Yin; Hee Dong Park; Min Hee Kang; Jin Tae Hong; Myung Koo Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  66     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-17     Completed Date:  2003-11-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1787-95     Citation Subset:  IM    
College of Pharmacy, and Research Center for Bioresource and Health, Chungbuk National University, San 48, Kaeshin-Dong, Heungduk-Ku, Cheongju 361-763, South Korea.
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MeSH Terms
Acetylcysteine / pharmacology
Adenosine Triphosphate / metabolism
Cell Survival / drug effects
Dopamine Agents / pharmacology
Drug Interactions
Levodopa / pharmacology*
Oxidative Stress / drug effects
PC12 Cells
Reactive Oxygen Species / metabolism
Tetrahydropapaveroline / pharmacology*
Reg. No./Substance:
0/Dopamine Agents; 0/Levodopa; 0/Reactive Oxygen Species; 4747-99-3/Tetrahydropapaveroline; 56-65-5/Adenosine Triphosphate; 616-91-1/Acetylcysteine

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