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Titolo:
L-DOPA CYTOTOXICITY TO PC12 CELLS IN CULTURE IS VIA ITS AUTOXIDATION
Autore:
BASMA AN; MORRIS EJ; NICKLAS WJ; GELLER HM;
Indirizzi:
UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOL,675 HOES LANE PISCATAWAY NJ 08854 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOLPISCATAWAY NJ 08854 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT NEUROL PISCATAWAY NJ 08854
Titolo Testata:
Journal of neurochemistry
fascicolo: 2, volume: 64, anno: 1995,
pagine: 825 - 832
SICI:
0022-3042(1995)64:2<825:LCTPCI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ASPARTATE GLUTAMATERGIC AGONIST; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; 2'-ETHYLPHENYL)-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED TOXICITY; SUPEROXIDE-DISMUTASE; FREE-RADICALS; 6-HYDROXYDOPAMINE; LINE; GROWTH; IRON;
Keywords:
NEUROTOXICITY; DOPAMINE; PARKINSONS DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
A.N. Basma et al., "L-DOPA CYTOTOXICITY TO PC12 CELLS IN CULTURE IS VIA ITS AUTOXIDATION", Journal of neurochemistry, 64(2), 1995, pp. 825-832

Abstract

The mechanism of cytotoxicity of L-DOPA was studied in the rat pheochromocytoma PC12 cell line. The cytotoxicity of L-DOPA to PC12 cells was time and concentration dependent. Carbidopa, which inhibited the conversion of L-DOPA to dopamine, did not protect against L-DOPA cytotoxicity in PC12 cells. Furthermore, clorgyline, a selective inhibitor of monoamine oxidase type A, and pargyline, an inhibitor of both monoamine oxidase types A and B, both did not have an effect on L-DOPA toxicity. These findings suggest that cytotoxicity was not due to dopamine formed from L-DOPA. Catalase or superoxide dismutase each partially protected against L-DOPA toxicity in PC12 cells. In combination, the effects were synergistic and provided almost total protection against cytotoxicity. 6-Cyano-7-nitroquinoxaline-2,3-dione, an antagonist of non-NMDA receptors, did not protect against L-DOPA toxicity. These data suggest that toxicity of L-DOPA is most likely due to the action of free radicals formed as a result of its autoxidation. Furthermore, these findings suggest that patients on long-term L-DOPA therapy are potentially at risk from the toxic intermediates formed as a result of its autoxidation.

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Documento generato il 30/11/20 alle ore 06:49:41