Effect of the MAO-B inhibitor, MDL72974, on superoxide dismutase activity and lipid peroxidation levels in the mouse brain
✍ Scribed by C. Thiffault; R. Quirion; J. Poirier
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 81 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
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 ϩ 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.