6-hydroxydopamine increases hydroxyl free radical production and DNA damage in rat striatum.
Oxidative damage is considered to be an important factor of 6-hydroxydopamine (6-OHDA) toxicity. To address this issue, microdialysis probes were implanted 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 electrochemical detection. Additionally, striatal tissue was analysed for DNA base alterations using gas chromatography-mass spectrometry. 6-OHDA administration resulted in a rapid and substantial 6.6-fold increase in 2,3-DHBA formation and also increased levels of the modified DNA bases 5-hydroxycytosine, hypoxanthine and 2,6-diamino-4-hydroxy-5-formamidopyrimidine. Hydroxyl radical formation and DNA base alterations are early phenomena of 6-OHDA toxicity and provide clues to the processes that may be involved in the initiation of cell death in Parkinson's disease.
Ferger
B
B
Wolfson Centre for Age-Related Diseases, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College London, London SE1 1UL, UK.
Rose
S
S
Jenner
A
A
Halliwell
B
B
Jenner
P
P
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004249:DNA Damage; D008401:Gas Chromatography-Mass Spectrometry; D062385:Hydroxybenzoates / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D019271:Hypoxanthine / Q000378:metabolism; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018663:Adrenergic Agents; D062385:Hydroxybenzoates; D019271:Hypoxanthine; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; C017400:5-hydroxycytosine; D016627:Oxidopamine; D003596:Cytosine