Effect of the MAO-B inhibitor, MDL72974, on superoxide dismutase activity and lipid peroxidation levels in the mouse brain.
MDL72974 is a member of a series of MAO-B inhibitors to be used as potential therapeutic agents in the treatment of Parkinson's and Alzheimer's diseases. However, we have recently observed a reduction in the density of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra of mice treated with MDL72974. As oxidative stress is known to play a significant role in the nigrostriatal pathway, analysis of the relationship between TH+ cell losses induced by MDL72974 and by free radical production was investigated in the present study. Results demonstrate a significant increase in superoxide dismutase (SOD) activity, a key antioxidant, in the striatum and cerebellum of MDL72974-treated mice, presumably in response to free radical production. An increase in lipid peroxidation levels was also observed in the striatum of these animals in a manner which is consistent with oxidative stress-inducing agents. We therefore suggest that MDL72974 may be detrimental to dopaminergic neurons of the nigrostriatal pathway via free radical-mediated reactions.
Thiffault
C
C
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Quirion
R
R
Poirier
J
J
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002082:Butylamines / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism*
D000498:Allyl Compounds; D002082:Butylamines; D008996:Monoamine Oxidase Inhibitors; C058000:mofegiline; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase