The endogeneous formation of highly chlorinated tetrahydro-beta-carbolines as a possible causative mechanism in idiopathic Parkinson's disease.
The causative interrelationship between long-term, low level exposure to chlorinated volatile organic solvents (VOSs) and neurodegenerative diseases (polyneuropathy, encephalopathy) are still an issue of controversial debate. Endogeneously formed chlorinated tetrahydro-beta-carbolines found by Bringmann 1995 (TaClo hypothesis) may contribute, in particular, to the development of (idiopathic) Parkinson's disease (PD) in the presence of the sufficient amount of trichloroacetaldehyde, an intermediate in metabolism of trichloroethylene (TRI). Long-term storage of specific VOSs over years, evident frrom exhalation pattern during the postexposure period, may serve as a promoting factor to form continuously TaClo non-enzymatically from tryptamine and trichloroacetaldehyde. Thus, the induction of TaClo-mediated neurotoxic processes extends over years. The onset of Parkinson's disease in three chronic TRI-exposed individuals during the postexposure period could be associated with the presence of TaClo in ng-range. Consequently, determination of TaClo and its derivatives in blood of humans exposed to chlorinated VOSs may serve as a marker of risk indicating either causative or supportive processes of neurodegeneration that may lead to manifestation of PD after many years.
Kochen
Walter
W
Children's Hospital, Clinical Chemistry, University of Heidelberg, Germany. walter.kochen@urz.uni-heidelberg.de
Kohlmüller
Dirk
D
De Biasi
Peter
P
Ramsay
Ray
R
D000368:Aged; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000378:metabolism* / Q000633:toxicity; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000209:etiology / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014241:Trichloroethylene / Q000378:metabolism / Q000633:toxicity
D002243:Carbolines; D009498:Neurotoxins; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D014241:Trichloroethylene; D012701:Serotonin; D004298:Dopamine