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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1993-2-19
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pubmed:abstractText |
Autoxidation and various enzyme-mediated oxidations of the serotonergic neurotoxin 5,7-dihydroxytryptamine (1) give 5-hydroxytryptamine-4,7-dione (2) and 6,6'-bi(5-hydroxytryptamine-4,7-dione) (3) as the major products. When administered into the ventricular system of mice 2 and 3 are general toxins. The LD50 values for 2 (29.6 +/- 0.04 micrograms) and 3 (25.4 +/- 0.30 micrograms) are lower than that for 1 (51.8 +/- 0.28 micrograms). In the presence of cellular reductants (glutathione, cysteine, ascorbate) and molecular oxygen, or when incubated with rat brain homogenate, 2 and 3 redox cycle and form superoxide radical anion, O2.-, as a byproduct. The lethal effects of 2 and 3 when introduced into the brain may in part be due to such redox cycling reactions which deplete oxygen levels and, as a result of Haber-Weiss chemistry deriving from O2.-, form the cytotoxic hydroxyl radical (HO.). Intraventricular administration of 2 and 3 to mice causes only relatively minor and transient (ca. 1 h to 1 day) changes in whole brain levels of dopamine, 5-hydroxytryptamine (from both 2 and 3), acetylcholine, and choline (from 2 only). These changes differ from the profound and long-lasting serotonergic deficit evoked by 1. On the basis of these results a hypothesis has been formulated which proposes that the selective neurotoxicity of 1 derives from its rapid uptake into serotonergic neurons where it is oxidatively converted to 2 and 3. Redox cycling reactions of 2 and 3 then result in the depletion of intraneuronal oxygen and concomitant formation of O2.-. Dismutation of O2.- gives H2O2 which, as a result of transition metal ion-catalyzed Haber-Weiss chemistry, yields HO.. Thus, neuronal damage and death might result from the combined effects of hypoxia and HO. formation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5,7-Dihydroxytryptamine,
http://linkedlifedata.com/resource/pubmed/chemical/Indolequinones,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotransmitter Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
229-36
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8093735-5,7-Dihydroxytryptamine,
pubmed-meshheading:8093735-Animals,
pubmed-meshheading:8093735-Brain,
pubmed-meshheading:8093735-Chromatography, High Pressure Liquid,
pubmed-meshheading:8093735-Indolequinones,
pubmed-meshheading:8093735-Lethal Dose 50,
pubmed-meshheading:8093735-Male,
pubmed-meshheading:8093735-Mice,
pubmed-meshheading:8093735-Neurotoxins,
pubmed-meshheading:8093735-Neurotransmitter Agents,
pubmed-meshheading:8093735-Oxidation-Reduction,
pubmed-meshheading:8093735-Oxygen Consumption,
pubmed-meshheading:8093735-Rats,
pubmed-meshheading:8093735-Rats, Wistar,
pubmed-meshheading:8093735-Serotonin
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pubmed:year |
1993
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pubmed:articleTitle |
Further insights into the molecular mechanisms of action of the serotonergic neurotoxin 5,7-dihydroxytryptamine.
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pubmed:affiliation |
Department of Chemistry and Biochemistry, University of Oklahoma, Norman 73019-0370.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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