CATECHOL IS THE MAJOR PRODUCT OF SALICYLATE HYDROXYLATION IN 1-METHYL-4-PHENYLPYRIDINIUM ION TREATED RATS

Salicylate hydroxylation using hydroxyl free radicals results into for mation of 2,3-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and cat echol. Inspite of the fact that in vitro experiments have shown that c atechol is a minor product, we have shown by these in vivo studies tha t it is a substantial product. Since catechol as well as 2,3-dihydroxy benzoic acid have not been found to be produced enzymatically from sal icylates, they appear useful as in vivo indicators for monitoring hydr oxyl free radicals. Administration of 1-methyl-4-phenylpyridinium ion (MPP+) to rat striatum using microdialysis results into the formation of hydroxyl radicals. Salicylate perfusion enables the estimation of t he three derivatives cited above. They increase d significantly after MPP+ administration in comparison to the baseline values, with catecho l. being the most significant. The maximum amounts were achieved 60 mi n after MPP+ administration, and the mean percentage increase at this time point were 83.1% for 2,3-DBA (n = 6, P = 0.005), 81.25% for 2,5-D BA (n = 6, P = 0.011) and 1228.8 % for catechol (n = 4, p = 0.00008). MPP+ caused substantial decrease of dopamine metabolites. Dihydroxyphe nylacetic acid decreased to 13% and homovanillic acid t o 11.4%. We co nclude that catechol is an important indicator of hydroxyl free radica l formation in this animal model which is well suited to study the rol e of free radicals in Parkinsonism.