European journal of drug metabolism and pharmacokinetics vol:23 issue:2 pages:137-42
Salicylate hydroxylation using hydroxyl free radicals results into formation of 2,3-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and catechol. Inspite of the fact that in vitro experiments have shown that catechol is a minor product, we have shown by these in vivo studies that it is a substantial product. Since catechol as well as 2,3-dihydroxybenzoic acid have not been found to be produced enzymatically from salicylates, they appear useful as in vivo indicators for monitoring hydroxyl 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 the three derivatives cited above. They increased significantly after MPP+ administration in comparison to the baseline values, with catechol being the most significant. The maximum amounts were achieved 60 min 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-DBA (n = 6, P = 0.011) and 1228.8% for catechol (n = 4, p = 0.00008). MPP+ caused substantial decrease of dopamine metabolites. Dihydroxyphenylacetic acid decreased to 13% and homovanillic acid to 11.4%. We conclude that catechol is an important indicator of hydroxyl free radical formation in this animal model which is well suited to study the role of free radicals in Parkinsonism.