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

Neuroreport
B FergerPeter Jenner

Abstract

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.

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Citations

Feb 26, 2004·Biochimica Et Biophysica Acta·Zuo-Hui ShaoChun-Su Yuan
May 17, 2005·Neuroscience Letters·Carmen NoelkerRichard Dodel
Nov 7, 2003·Journal of Chromatography. a·Qingjiang WangYuzhi Fang
Nov 27, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Fu-Chou ChengTung-Hu Tsai
Jul 28, 2011·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Yoshinori Masuo, Masami Ishido
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May 24, 2006·Free Radical Biology & Medicine·Kok Seong LimBarry Halliwell
Aug 26, 2015·Neurología : publicación oficial de la Sociedad Española de Neurología·D Hernandez-BaltazarA Villanueva-Olivo
Nov 2, 2011·Neuroscience Letters·Chiara MencarelliPilar Martinez-Martinez
Feb 19, 2005·Journal of Applied Physiology·Edwin B YanDavid W Walker
Jun 16, 2021·Chemical Society Reviews·Barry HalliwellMiral Dizdaroglu

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