6-hydroxydopamine increases hydroxyl free radical production and DNA damage in rat striatum

Oxidative damage is considered to be an important factor of 6-hydroxydopami ne (6-OHDA) toxicity. To address this issue, microdialysis probes were impl anted into the striatum of Wistar rats and perfused with 6-OHDA. Salicylate was included in the perfusion fluid to measure 2,3-dihydroxybenzoic acid ( 2,3-DHBA) as a marker of hydroxyl radical formation using HPLC with electro chemical detection. Additionally, striatal tissue was analysed for DNA base alterations using gas chromatography-mass spectrometry. 6-OHDA administrat ion resulted in a rapid and substantial 6.6-fold increase in 2,3-DHBA forma tion and also increased levels of the modified DNA bases 5-hydroxycytosine, hypoxanthine and 2,6-diamino-4-hydroxy-5-formamidopyrimidine. Hydroxyl rad ical formation and DNA base alterations are early phenomena of 6-OHDA toxic ity and provide clues to the processes that may be involved in the initiati on of cell death in Parkinson's disease. NeuroReport 12:1155-1159 (C) 2001 Lippincott Williams & Wilkins.