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Effect of the MAO‐B inhibitor, MDL72974, on superoxide dismutase activity and lipid peroxidation levels in the mouse brain
Author(s) -
Thiffault C.,
Quirion R.,
Poirier J.
Publication year - 1998
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199803)28:3<208::aid-syn3>3.0.co;2-e
Subject(s) - substantia nigra , superoxide dismutase , striatum , oxidative stress , lipid peroxidation , chemistry , nigrostriatal pathway , tyrosine hydroxylase , dopaminergic , free radical theory of aging , medicine , biochemistry , pharmacology , endocrinology , dopamine , biology , enzyme
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. Synapse 28:208–211, 1998. © 1998 Wiley‐Liss, Inc.